SIGN 136 - Management of Chronic Pain

SIGN 136 • Management of chronic pain
A national clinical guideline First published December 2013

Revised edition published August 2019
Evidence
KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS
LEVELS OF EVIDENCE
1++ High-quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias
1- Meta-analyses, systematic reviews, or RCTs with a high risk of bias
High-quality systematic reviews of case-control or cohort studies
2++
High-quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the
relationship is causal
Well-conducted case-control or cohort studies with a low risk of confounding or bias and a moderate probability that the
2+
relationship is causal
2- Case-control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, eg case reports, case series

4 Expert opinion
GRADES OF RECOMMENDATION
Note: The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the
clinical importance of the recommendation.
t least one meta-analysis, systematic review, or RCT rated as 1++,
A
and directly applicable to the target population; or
A
body of evidence consisting principally of studies rated as 1+,
A
directly applicable to the target population, and demonstrating overall consistency of results
A body of evidence including studies rated as 2++,
B irectly applicable to the target population, and demonstrating overall consistency of results; or
d
Extrapolated evidence from studies rated as 1++ or 1+
A body of evidence including studies rated as 2+,
C directly applicable to the target population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
Evidence level 3 or 4; or
D
Extrapolated evidence from studies rated as 2+
GOOD PRACTICE POINTS
 Recommended best practice based on the clinical experience of the guideline development group
NHS Evidence has accredited the process used by Scottish Intercollegiate Guidelines
Network to produce guidelines. Accreditation is applicable to guidance produced using
the processes described in SIGN 50: a guideline developer’s handbook, 2008 edition
www.sign.ac.uk/sign-50.html. More information on accreditation can be viewed at
www.evidence.nhs.uk
Healthcare Improvement Scotland (HIS) is committed to equality and diversity and assesses all its publications for likely impact on the
six equality groups defined by age, disability, gender, race, religion/belief and sexual orientation.
SIGN guidelines are produced using a standard methodology that has been equality impact assessed to ensure that these equality
aims are addressed in every guideline. This methodology is set out in the current version of SIGN 50, our guideline manual, which can
be found at www.sign.ac.uk/sign-50.html. The EQIA assessment of the manual can be seen at www.sign.ac.uk/assets/sign50eqia.
pdf. The full report in paper form and/or alternative format is available on request from the Healthcare Improvement Scotland Equality
and Diversity Officer.
Every care is taken to ensure that this publication is correct in every detail at the time of publication. However, in the event of errors
or omissions corrections will be published in the web version of this document, which is the definitive version at all times. This version
can be found on our web site www.sign.ac.uk.
This document is produced from elemental chlorine-free material and is sourced from sustainable forests.
Scottish Intercollegiate Guidelines Network
Management of chronic pain

A national clinical guideline
First published December 2013

Scottish Intercollegiate Guidelines Network

Gyle Square, 1 South Gyle Crescent
Edinburgh EH12 9EB
www.sign.ac.uk
First published December 2013

ISBN 978 1 909103 16 0
Citation text
Scottish Intercollegiate Guidelines Network (SIGN).
Management of chronic pain. Edinburgh: SIGN; 2013.
(SIGN publication no. 136). [December 2013]. Available from URL: http://www.sign.ac.uk
This document is licensed under the Creative Commons Attribution-Noncommercial-NoDerivatives 4.0

International Licence. This allows for the copy and redistribution of this document as long as SIGN is fully
acknowledged and given credit. The material must not be remixed, transformed or built upon in any way.
To view a copy of this licence, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
Contents
Contents
1 Introduction.......................................................................................................................................................................1
1.1 The need for a guideline....................................................................................................................................................................... 1
1.2 Remit of the guideline........................................................................................................................................................................... 1
1.3 Definitions.................................................................................................................................................................................................. 2
1.4 Reporting in pain trials.......................................................................................................................................................................... 2
1.5 Statement of intent................................................................................................................................................................................. 3
2 Key recommendations.....................................................................................................................................................5
2.1 Assessment and planning of care...................................................................................................................................................... 5
2.2 Supported self management.............................................................................................................................................................. 5
2.3 Pharmacological management.......................................................................................................................................................... 5
2.4 Psychologically based interventions................................................................................................................................................ 5
2.5 Physical therapies.................................................................................................................................................................................... 5
3 Assessment and planning of care..................................................................................................................................6
3.1 Assessment tools..................................................................................................................................................................................... 6
3.2 Timing of intervention........................................................................................................................................................................... 6
3.3 Care management................................................................................................................................................................................... 7
3.4 Patient-professional interaction......................................................................................................................................................... 7
4 Supported self management.........................................................................................................................................8
5 Pharmacological therapies.............................................................................................................................................9
5.1 Introduction............................................................................................................................................................................................... 9
5.2 Non-opioid analgesics (simple and topical)................................................................................................................................... 10
5.3 Opioids........................................................................................................................................................................................................ 12
5.4 Antiepilepsy drugs.................................................................................................................................................................................. 17
5.5 Antidepressants........................................................................................................................................................................................ 18
5.6 Combination therapies.......................................................................................................................................................................... 20
6 Psychologically based interventions............................................................................................................................22
6.1 Multidisciplinary pain management programmes...................................................................................................................... 22
6.2 Unidisciplinary education..................................................................................................................................................................... 23
6.3 Behavioural therapies............................................................................................................................................................................ 24
6.4 Cognitive behavioural therapy........................................................................................................................................................... 25
6.5 Mindfulness meditation and acceptance and commitment therapy................................................................................... 26
7 Physical therapies.............................................................................................................................................................27
7.1 Manual therapy........................................................................................................................................................................................ 27
7.2 Exercise........................................................................................................................................................................................................ 28
7.3 Traction........................................................................................................................................................................................................ 30
7.4 Electrotherapy........................................................................................................................................................................................... 30
8 Complementary therapies..............................................................................................................................................31
8.1 Acupuncture.............................................................................................................................................................................................. 31
8.2 Herbal medicine....................................................................................................................................................................................... 31
8.3 Other therapies......................................................................................................................................................................................... 32
Managementofofchronic
Management chronic pain
pain
9 Dietary therapies..............................................................................................................................................................33
10 Provision of information.................................................................................................................................................34
10.1 Sources of further information........................................................................................................................................................... 34
10.2 Checklist for provision of information.............................................................................................................................................. 36
11 Implementing the guideline...........................................................................................................................................37
11.1 Implementation strategy...................................................................................................................................................................... 37
11.2 Resource implications of key recommendations......................................................................................................................... 37
11.3 Auditing current practice...................................................................................................................................................................... 37
11.4 Additional advice to NHSScotland from Healthcare Improvement Scotland and
the Scottish Medicines Consortium................................................................................................................................................. 38
12 The evidence base............................................................................................................................................................39
12.1 Systematic literature review................................................................................................................................................................. 39
12.2 Recommendations for research......................................................................................................................................................... 39
12.3 Review and updating............................................................................................................................................................................. 40
13 Development of the guideline.......................................................................................................................................41
13.1 Introduction............................................................................................................................................................................................... 41
13.2 The guideline development group................................................................................................................................................... 41
13.3 Consultation and peer review............................................................................................................................................................. 42
Abbreviations.................................................................................................................................................................................44
Annex 1............................................................................................................................................................................................46
Annex 2............................................................................................................................................................................................50
Annex 3 ...........................................................................................................................................................................................54
Annex 4............................................................................................................................................................................................56
Annex 5............................................................................................................................................................................................62
References......................................................................................................................................................................................63
1 • Introduction
1 Introduction
1.1 THE NEED FOR A GUIDELINE
Chronic pain is a major clinical challenge: across Europe approximately 18% of the population are currently
affected by moderate to severe chronic pain.1 It has a considerable impact on quality of life, resulting in
significant suffering and disability.2-4 While in many cases it is accepted that a cure is unlikely, the impact on
quality of life, mood and function can be significantly reduced by appropriate measures. Chronic pain not only
has an impact on affected individuals and their families, it also has substantial economic costs. For example,
back pain alone was estimated to cost £12 billion per annum in the UK in 1998, and arthritis-associated pain
costs around 2.5% of the gross national product of Western nations.5,6
While a proportion of patients will require access to specialist secondary and tertiary care pain services, the
majority of patients will be managed in the community or primary care. It is vital that general practitioners
(GPs) and other healthcare professionals have the best possible resource and support to manage their patients
properly and have facilities for accessing appropriate specialist services when required. Within Scotland there is
evidence of wide variation in clinical practice service and resource provision, with a general lack of knowledge
about chronic pain and the management options that are available.7
A wide range of both pharmacological and non-pharmacological management strategies are available for
chronic pain. The challenge is to understand the extensive published evidence for different treatments and
to determine when and where to use them for the best long-term outcomes for the patient. It is hoped that
this evidence based guideline will provide the information needed to improve clinical outcomes and quality
of life for patients with chronic pain.
1.2 REMIT OF THE GUIDELINE
1.2.1 OVERALL OBJECTIVES

This guideline provides recommendations based on current evidence for best practice in the assessment
and management of adults with chronic non-malignant pain in non-specialist settings.
It does not cover:
y interventions which are only delivered in secondary care.
y treatment of patients with headache
y children. Treatment options for children with chronic pain are different to those of adults (see the Scottish
Government guideline, management of chronic pain in children and young people 2018, available from
www.sign.ac.uk/assets/chronic_pain_in_children.pdf.pdf).8
yy underlying conditions. Chronic pain is caused by many underlying conditions. The treatment of these
conditions is not the focus of this guideline so the search strategies were restricted to the treatment of
chronic pain, not specific conditions.
Details of the literature review are covered in section 12 and the key questions used to develop the guideline
can be found in Annex 1. SIGN guidelines on other relevant topics are available on the SIGN website,
www.sign.ac.uk.9-12
1.2.2 TARGET USERS OF THE GUIDELINE

This guideline will be of particular interest to all healthcare professionals involved in the assessment and
management of patients with chronic pain, including general practitioners, pharmacists, anaesthetists,
psychologists, psychiatrists, physiotherapists, rheumatologists, occupational therapists, nurses, patients,
carers and voluntary organisations with an interest in chronic pain.
|1
1.2.3 SUMMARY OF UPDATES TO THE GUIDELINE, BY SECTION
5.3 Opioids Completely revised (2019)

12.2 Recommendations for research Opioid recommendations
updated (2019)
Annex 4 Pathway for using strong opioids in patients Updated (2019)
with chronic pain
1.3 DEFINITIONS
In this guideline chronic pain is defined as pain that has been present for more than 12 weeks.
The non-specialist setting is any setting where the training and infrastructure is not specifically designed
for treating chronic pain. This might include management in the community, primary care or secondary
care.
1.4 REPORTING IN PAIN TRIALS

Difficulties in reporting make the interpretation of the evidence base challenging. Pain is defined by the
International Association for the Study of Pain as “an unpleasant sensory or emotional experience associated
with actual or potential tissue damage, or described in terms of such damage”.13 Chronic pain is a complex
phenomenon with consequent challenges for its assessment and management both in clinical trials and
routine clinical practice. This is further complicated by the fact that even in the same condition there may
be quite different pain mechanisms among patients. While changes in the peripheral pain processing might
predominate in one patient, central changes may be much more important in the next patient.14-16 While a
particular treatment may work very effectively in one patient, it may not work at all in another patient with
the same condition. In clinical trials, unless there is careful assessment of the chronic pain syndrome in each
patient, potentially useful treatments may be discarded as being ineffective when the average response is
considered. Even good-quality, adequately-powered double-blinded randomised controlled trials may not
provide the best approach for developing a strong evidence base for pain management.17-19
These limitations have been recognised internationally, leading to the development of the Initiative on
Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT, www.immpact.org) in 2002.
A number of factors need to be considered in order to optimise the design of trials studying chronic pain.
These include patient selection (pain diagnosis, duration, intensity) and sample size, different phases within
the trial (eg enriched enrolment) and duration of study, treatment groups (including active versus inactive
placebo comparator), dosing strategies (fixed versus flexible) and type of trial (eg parallel, crossover).17,20,21
To allow comparison between studies a standardised approach to outcome measures, is recommended by
IMMPACT.17 Four key domains are recommended to adequately assess outcomes:
1. Pain intensity. A numerical rating scale 0-10 is recommended as the most practical and sensitive.
2. Physical functioning. Assessment with validated self-report questionnaires such as the Multidimensional
Pain Inventory or Brief Pain Inventory interference scales is recommended.
3. Emotional functioning. The Beck Depression Inventory and the Profile of Mood States are recommended.
4. Patient rating of overall improvement. The Patient Global Impression of Change scale can be used.
Side effects and detailed information about patient recruitment and progress through the trial should also
be recorded.22,23
While much of the literature published to date does provide a sound evidence base for this guideline, it is
hoped that future studies will follow the IMMPACT recommendations.
2|
1 • Introduction
In addition to the limitations of assessment and trial design, concerns have been raised about how analysis
methods may either obscure clinically important positive outcomes, or overestimate treatment effects. If
the average response is considered, a treatment may appear ineffective, whereas it could have the potential
to be effective in a particular subgroup of the patients being studied. It may, therefore, be useful to analyse
responders to a particular treatment separately from non-responders.19
Another important factor is how patients who drop out before completing the study are dealt with in
the analysis. Using the last-observation-carried-forward (LOCF) for patients who drop out is based on the
assumption that in a randomised controlled trial (RCT) drop outs will occur randomly between the treatment
groups. The active treatment may be an effective analgesic but if it has an unpleasant side effect profile then
drop outs are likely to be higher in a non-random manner in this treatment group. Pain scores prior to drop
out may therefore demonstrate efficacy, but in clinical practice this treatment is unlikely to be tolerated.
The majority of RCTs use the imputation method of LOCF, and may therefore potentially overestimate the
treatment effect.24
While there are a number of good-quality systematic reviews and meta-analyses that provide an evidence base
for the management of patients with chronic pain, there are some limitations with the currently published
literature. This has been taken into consideration by the guideline development group when appraising
the evidence and, where there are areas of potential doubt, recommendations have been downgraded
accordingly. Further details of the literature review can be found in section 12.
1.5 STATEMENT OF INTENT

This guideline is not intended to be construed or to serve as a standard of care. Standards of care are
determined on the basis of all clinical data available for an individual case and are subject to change
as scientific knowledge and technology advance and patterns of care evolve. Adherence to guideline
recommendations will not ensure a successful outcome in every case, nor should they be construed as
including all proper methods of care or excluding other acceptable methods of care aimed at the same
results. The ultimate judgement must be made by the appropriate healthcare professional(s) responsible
for clinical decisions regarding a particular clinical procedure or treatment plan. This judgement should only
be arrived at through a process of shared decision making with the patient, covering the diagnostic and
treatment choices available. It is advised, however, that significant departures from the national guideline
or any local guidelines derived from it should be fully documented in the patient’s medical records at the
time the relevant decision is taken.
1.5.1 PATIENT VERSION

A patient version of this guideline is available from the SIGN website, www.sign.ac.uk
1.5.2 PRESCRIBING OF LICENSED MEDICINES OUTWITH THEIR MARKETING AUTHORISATION

Recommendations within this guideline are based on the best clinical evidence. Some recommendations
may be for medicines prescribed outwith the marketing authorisation (MA) also known as product licence.
This is known as ‘off label’ use.
Medicines may be prescribed off label in the following circumstances:
yy for an indication not specified within the marketing authorisation
yy for administration via a different route
yy for administration of a different dose
yy for a different patient population.
An unlicensed medicine is a medicine which does not have MA for medicinal use in humans.
Generally the off label use of medicines becomes necessary if the clinical need cannot be met by licensed
medicines within the marketing authorisation. Such use should be supported by appropriate evidence and
experience.25
|3
“Prescribing medicines outside the conditions of their marketing authorisation alters (and probably increases)
the prescribers’ professional responsibility and potential liability”.25
The General Medical Council (GMC) recommends that when prescribing a medicine off label, doctors should:
yy b e satisfied that such use would better serve the patient’s needs than an authorised alternative (if one
exists).
yy be satisfied that there is sufficient evidence/experience of using the medicines to show its safety and
efficacy, seeking the necessary information from appropriate sources.
yy record in the patient’s clinical notes the medicine prescribed and, when not following common practice,
the reasons for the choice.
yy take responsibility for prescribing the medicine and for overseeing the patient’s care, including monitoring
the effects of the medicine.
Non-medical prescribers should ensure that they are familiar with the legislative framework and their own
professional prescribing standards.
Prior to any prescribing, the licensing status of a medication should be checked in the summary of product
characteristics (SPC).26 The prescriber must be competent, operate within the professional code of ethics of
their statutory bodies and the prescribing practices of their employers.27
1.5.3 ADDITIONAL ADVICE TO NHSSCOTLAND FROM HEALTHCARE IMPROVEMENT SCOTLAND AND THE
SCOTTISH MEDICINES CONSORTIUM
Healthcare Improvement Scotland processes multiple technology appraisals (MTAs) for NHSScotland that
have been produced by the National Institute for Health and Care Excellence (NICE) in England and Wales.
The Scottish Medicines Consortium (SMC) provides advice to NHS boards and their Area Drug and Therapeutics
Committees about the status of all newly licensed medicines and any major new indications for established
products.
SMC advice relevant to this guideline is summarised in section 11.4.
4|
2 • Key recommendations
2 Key recommendations
The following recommendations were highlighted by the guideline development group as the key clinical
recommendations that should be prioritised for implementation. The grade of recommendation relates to the
strength of the supporting evidence on which the recommendation is based. It does not reflect the clinical
importance of the recommendation.
2.1 ASSESSMENT AND PLANNING OF CARE
99 concise history, examination and biopsychosocial assessment, identifying pain type (neuropathic/
A
nociceptive/mixed), severity, functional impact and context should be conducted in all patients with
chronic pain. This will inform the selection of treatment options most likely to be effective.
2.2 SUPPORTED SELF MANAGEMENT
99 ealthcare professionals should signpost patients to self-help resources, identified and recommended
H
by local pain services, as a useful aide at any point throughout the patient journey. Self management
may be used from an early stage of a pain condition through to use as part of a long-term management
strategy.
2.3 PHARMACOLOGICAL MANAGEMENT
99 atients using analgesics to manage chronic pain should be reviewed at least annually, and more
P
frequently if medication is being changed, or the pain syndrome and/or underlying comorbidities alter.
2.4 PSYCHOLOGICALLY BASED INTERVENTIONS
C
Referral to a pain management programme should be considered for patients with chronic pain.
99 linicians should be aware of the possibility that their own behaviour, and the clinical environment,
C
can impact on reinforcement of unhelpful responses.
2.5 PHYSICAL THERAPIES
B
Exercise and exercise therapies, regardless of their form, are recommended in the management
of patients with chronic pain.
A
Advice to stay active should be given in addition to exercise therapy for patients with chronic low
back pain to improve disability in the long term. Advice alone is insufficient.
|5
3 Assessment and planning of care

3.1 ASSESSMENT TOOLS
There is consensus that it is good practice to assess severity, impact and type of pain before the initiation of
treatment, to guide management and gauge its success.28,29 No evidence was identified that the use of any 4
assessments had any effect on clinically relevant outcomes.
Brief and well-validated tools are available for the assessment of pain in non-specialist settings. These include
tools to measure severity of pain and/or its functional impact, tools to identify neuropathic pain, and tools
to predict risk of chronicity in acute pain presentations.
One RCT of the STartBack tool stratified patients with back pain into low, medium and high risk of poor
prognosis, to inform and evaluate treatment outcomes.30 Those at medium risk were referred for physiotherapy
and those at high risk were referred for psychologically augmented physiotherapy. Sixty per cent of patients
in the intervention group and 58% in the control group had chronic pain. Outcome was measured using 1++
the Roland Morris Disability Questionnaire (RMDQ) scores, range 0 (no disability) to 24 (severe disability).
At four months the intervention group reported an adjusted mean change of RMDQ score of 4.7 (standard
deviation (SD) 5.9) compared to the control group (3.0 (SD 5.9)) with a between-group difference of 1.81
(95% confidence interval (CI) 1.06 to 2.57). Scores at 12 months were 4.3 (SD 6.4) versus 3.3 (SD 6.2), between-
group difference 1.06 (95% CI 0.25 to 1.86).30
99 concise history, examination and biopsychosocial assessment, identifying pain type (neuropathic/
A
nociceptive/mixed), severity, functional impact and context should be conducted in all patients with
chronic pain. This will inform the selection of treatment options most likely to be effective.
A pathway for assessment can be found in Annex 2.
3.2 TIMING OF INTERVENTION

The specialist resource available for managing chronic pain is limited and long waits between the onset of
pain, diagnosis of chronic pain, referral and seeing a specialist are common.
99 eferral should be considered when non-specialist management is failing, chronic pain is poorly
R
controlled, there is significant distress, and/or where specific specialist intervention or assessment is
considered.
A systematic review of observational studies concluded that longer delays between specialist referral and
specialist consultation result in poorer health and pain management by the time of this consultation. This 2++
deterioration starts as early as five weeks from referral and there is consensus that a delay of longer than six
months is medically unacceptable.31
No RCT evidence was found that early or late initiation of specific treatments or early or late specialist referral
influences outcome in patients with chronic pain.
6|
3 • Assessment and planning of care
3.3 CARE MANAGEMENT

Care management encompasses the assessment of a patient’s needs, development of an individualised care
plan, management of access to other services, and the monitoring and reassessment of those needs.32 Care
management strategies are used in primary care for many chronic diseases and are intended to improve the
quality of care and the use of resources.
A randomised controlled trial studied a collaborative care programme which included clinician education,
patient assessment, education, goal setting and two-monthly telephone follow up by a primary care based pain
team (who had minimal previous pain management experience), and communication of recommendations to 1++
GPs. This intervention led to statistically significant but modest reductions in the primary outcomes of mean
pain-related disability, pain and depression scores. The number of patients with a 30% reduction in pain-related
disability was clinically and statistically superior in the intervention group (21.9% versus 14% in the control
group; p=0.04). This was a secondary outcome, however, and the results were not well reported.33
Another RCT studied an implementation strategy to promote a national guideline for management of back pain,
with or without motivational counselling from practice nurses. This study showed improvements in outcomes 1+
but these were small, inconsistent and of unconvincing clinical significance.34
A review of nurse-led care identified only two RCTs in primary care which were of insufficient quality to support
1-
any recommendations.35
Another review found that evidence for the use of computerised clinical decision support systems was too
2-
weak to draw any conclusions.36
Many studies demonstrated that other care-management approaches are feasible but with significant resource
implications, and no evidence of clinically significant improvement in outcomes.
3.4 PATIENT-PROFESSIONAL INTERACTION

Studies suggest that, for patients with chronic pain, person-centred approaches, involvement in decision
making, and concordance with professionals generally enhance the consultation experience. There is no high- 3
quality evidence directly linking the nature of the interaction between healthcare professionals and patients to 1-
outcomes in chronic pain management. Specific training of professionals in adopting these approaches might 2+
1+
improve outcomes such as patient satisfaction with the interaction, reduction in anxiety and reduction in pain
2++
levels.37-42 Further evidence that this effort and investment leads to long-term improved health outcomes is
required before their widespread adoption.43
99
A compassionate, patient-centred approach to assessment and management of chronic pain is likely
to optimise the therapeutic environment and improve the chances of successful outcome.
|7
4 Supported self management

Self-management programmes are safe, low technology, community-based and affordable interventions to
help patients better manage their condition.44 Patient or lay self-help or self-management therapies are distinct
from simple patient education or skills training. They are structured programmes which aim to allow people +
1
to take an active part in the management of their own chronic condition.45 These programmes are primarily
educational, addressing self management and delivered by lay people. The form of delivery can be in groups
or as individuals, face-to-face, by post, or electronically. The essential component is that it involves interaction
between a participant and a tutor.
Participation in a self-management programme was found to reduce pain (standardised mean difference (SMD)
-0.14, 95% CI -0.23 to -0.04) and disability (-0.17, 95% CI -0.27 to -0.07) in patients with arthritis for up to twelve 1
+
months. Insufficient evidence was found to determine the effectiveness in patients with chronic low back pain.44
The use of internet-based self-help materials can be a beneficial adjunct to clinical care for short-term pain
relief, reduction in perceived disability, and improvement in stress, coping and social support.46-49 Outcomes 1
+
for these studies varied, but overall improvements were small.

Studies on lay-led self-management education programmes for patients with a variety of long-term conditions
have shown a small short-term improvement in participants’ confidence to manage their own health
(SMD -0.3, 95% CI -0.41 to -0.19), adoption of aerobic exercises ( SMD -0.2, 95% CI -0.27 to -0.12) and well-being 1
+
(SMD -0.2, 95% CI -0.3 to-0.1). No evidence was found on the impact of the programmes on psychological
health, symptoms or health-related quality of life.45
Patients require advice and specific instructions on appropriate exercise(s) and/or restoration of functional +
1
activities to promote active self management. Simple advice is not sufficient.50
C
Self-management resources should be considered to complement other therapies in the treatment
99 ealthcare professionals should signpost patients to self-help resources, identified and recommended
H
by local pain services, as a useful aide at any point throughout the patient journey. Self management
may be used from an early stage of a pain condition through to use as part of a long-term management
strategy.
Sources of further information for patients can be found in Section 10.
8|
5 • Pharmacological therapies
5 Pharmacological therapies
5.1 INTRODUCTION
A wide range of analgesics have been used in the treatment of chronic pain. This section addresses their
individual use, but there are a number of more general aspects that should also be considered.
Although it was developed and validated only for the treatment of cancer pain, the World Health Organization
analgesic ladder is widely used to guide basic treatment of acute and chronic pain.51, 52 There is little good-
quality evidence for its use in chronic pain, but it does provide an analgesic strategy for non-specialists. Careful
assessment and diagnosis is key to initiating appropriate pharmacotherapy. Continuing success requires
regular, scheduled reassessment of pain relief and side effects (see Annex 2 for pathways on assessment and
managing care).
Figure 1: World Health Organization analgesic ladder53
Reproduced with permission from the World Health Organization

There is considerable variation in patient responses to analgesia, both in terms of efficacy and side effects.19
Even with the same chronic pain syndrome the underlying neurobiology will differ between individuals,
influencing analgesic response.16,54 There is also increasing evidence that variations in drug responses are
linked to genetic factors (eg opioids).55 Thus if a patient either fails to tolerate or has inadequate analgesia
from a drug, then it is worthwhile considering a different agent from the same class of drug.
It is useful to have an indication of when to stop a medication, particularly for antineuropathic agents where
there is a period of dose titration to response. If there has been no response to treatment within two to
four weeks, after titration to adequate dose, patients are unlikely to develop a response thereafter. Integral
to success is regular reassessment of the patient and stopping medication that is not working effectively.
There is a scientific basis for the use of polypharmacy due to the complex nature of pain neurobiology,
and evidence from acute pain where a combination of analgesics is used to improve postoperative pain
control.56 A Cochrane review of the use of combination therapies in patients with neuropathic pain found
good evidence for improved efficacy from two-drug combinations, but drop-out rates tended to be higher
because of increased adverse effects (see section 5.6).57
|9
Regardless of which analgesia is used, regular review and reassessment to determine that there is continued
value from using a particular medication is important in providing ongoing good-quality chronic pain
management.
99 atients using analgesics to manage chronic pain should be reviewed at least annually, and more
P
frequently if medication is being changed, or the pain syndrome and/or underlying comorbidities alter.
Prescribing advice to NHSScotland from the Scottish Medicines Consortium can be found in Section 11.4.
5.2 NON-OPIOID ANALGESICS (SIMPLE AND TOPICAL)
5.2.1 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Regular treatment with a non-steroidal anti-inflammatory drug (NSAID) has a modest beneficial effect in
patients with non-specific low back pain compared with placebo, with an overall improvement of about 10%. 1++
No difference has been observed between different NSAIDs or between non-selective and cyclo-oxygenase
(COX)-2 selective NSAIDs.58
A systematic review of six studies that compared various NSAIDs with paracetamol in low back pain found
a trend in favour of NSAID (pooled SMD -0.21, 95% CI -0.43 to 0.02) but this was not significant.58 One high- 1++
quality RCT within the review found NSAIDs to be superior to paracetamol. Adverse effects were more
common with NSAIDs than paracetamol (RR 1.76, 95% CI 1.12 to 2.76).
NSAID treatment is associated with a higher risk of adverse effects compared with placebo (relative risk
(RR) 1.24, 95% CI 1.07 to 1.43).58 Side effects were varied and included abdominal pain, diarrhoea, oedema, 1++
dry mouth, rash, dizziness, headache, and tiredness.58-60 COX-2 selective NSAIDs had fewer side effects than
traditional NSAIDs (RR 0.83, 95% CI 0.70 to 0.99).58
Gastrointestinal (GI) adverse effects are well-established risks of long-term regular NSAID treatment. This
has been compounded by emerging evidence showing an increased risk of cardiovascular disease, stroke
and heart failure. The risk of serious upper GI events differs significantly between NSAIDs.61 The greatest risk 2+
of upper GI bleeding/perforation is seen with non-selective NSAIDs; those with a long half-life and slow-
release preparations. The highest risk is with piroxicam (RR 9.94, 95% CI 5.99 to16.50) followed by naproxen
(RR 5.57, 95% CI 3.94 to 7.87) whereas COX-2 inhibitors such as celecoxib (RR 1.42, 95% CI 0.85 to 2.3) are
associated with the lowest risk.61
Meta-analyses of RCTs have shown that long-term regular use of ibuprofen, diclofenac, celecoxib and
etorocoxib are all associated with an increased risk of myocardial infarction and coronary heart disease death 1++
whereas this has not been observed with naproxen. In the same meta-analysis, all NSAIDs were associated
with an increased risk of heart failure, but there was no evidence of an increased risk of stroke.62
B
NSAIDs should be considered in the treatment of patients with chronic non-specific low back pain.
B
Cardiovascular and gastrointestinal risk needs to be taken into account when prescribing any
non-steroidal anti-inflammatory drug.
Further recommendations on the use of NSAIDs for specific conditions are available in guidelines focusing
on rheumatoid arthritis, osteoarthritis and gout.9, 63-66
10 |
5.2.2 PARACETAMOL
There is insufficient evidence to determine the efficacy of paracetamol in the treatment of patients with
generalised chronic low back pain.59,67 Paracetamol showed slightly inferior pain relief to NSAIDs in patients 1
++
with osteoporosis and chronic low back pain (SMD 0.3).59

Paracetamol (1,000 to 4,000 mg/day) showed a small benefit over placebo in treatment of patients with knee
and hip osteoarthritis (OA) pain and could be considered in addition to non-pharmacological treatments.68 ++
1
One study showed high-dose paracetamol (3,900 mg/day) to be more effective than placebo for pain relief 4
and improved function in patients with OA of the knee.68 NICE advise that paracetamol may be a suitable
adjunct to other treatments such as education or exercise.64
A combination of paracetamol 1,000 mg and ibuprofen 400 mg was significantly superior to regular
1+
paracetamol 1,000 mg alone for knee pain at 13 weeks but with an increased risk of gastrointestinal bleeding.69
C
Paracetamol (1,000-4,000 mg/day) should be considered alone or in combination with NSAIDs in the
management of pain in patients with hip or knee osteoarthritis in addition to non-pharmacological
treatments.
5.2.3 NEFOPAM
The evidence identified on the use of nefopam for chronic pain relief is not sufficient to support a ++
1
recommendation.70
5.2.4 TOPICAL NSAIDS

Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal
conditions.71 The best evidence was for topical diclofenac in osteoarthritis, where the number needed to treat
(NNT) for at least 50% pain relief over eight to 12 weeks compared with placebo was 6.4 for the diclofenac
solution (four studies n=1,006), and 11 for the diclofenac gel (four studies, n=2,120). It was not possible to 1++
calculate NNTs of other individual topical NSAIDs compared with placebo. There was no difference in efficacy
in a direct comparison of a topical NSAID with an oral NSAID. Local adverse events (mostly mild skin reactions)
were more common with topical NSAIDs compared with placebo or oral NSAIDs, but there was no increase
in serious adverse events. Gastrointestinal adverse events with topical NSAIDs did not differ from placebo,
but were less frequent than with oral NSAIDs.71
A
Topical NSAIDs should be considered in the treatment of patients with chronic pain from
musculoskeletal conditions, particularly in patients who cannot tolerate oral NSAIDs.
5.2.5 TOPICAL CAPSAICIN

Topical capsaicin is available as low-dose cream (0.025% or 0.075%) or as a high dose (8%) patch.
Few studies of low dose cream were identified but it appears to have no benefit over placebo cream for
patients with neuropathic pain.72 For patients with osteoarthritis three RCTs, ranging from four or twelve 1+
++
1
weeks in duration, found that low-dose capsaicin cream is better than placebo.73
In studies of patients with postherpetic neuralgia (PHN) and patients with human immunodeficiency virus
(HIV) neuropathy, application of an 8% patch gives significant benefit over placebo.74 In patients with PHN
the NNT was 7 (95% CI 4.6 to 15) for those who were better or very much better at 12 weeks. In patients 1++
with HIV neuropathy the NNT was 5.8 (95% CI 3.8 to 12) for those who were better or very much better at
12 weeks. Although of benefit, the cost and specialist application mean that it should be used when other
therapies have failed.
A
Topical capsaicin patches (8%) should be considered in the treatment of patients with peripheral
neuropathic pain when first-line pharmacological therapies have been ineffective or not tolerated.
| 11
5.2.6 TOPICAL LIDOCAINE

Topical lidocaine is better than placebo in treating patients with postherpetic neuralgia (p=0.003) based on ++
1
results from three RCTs.75,76
A systematic review on the use of lidocaine plaster for patients with refractory neuropathic pain (pain not
responding to a number of standard treatments) concluded that little evidence is available, results of studies
were inconsistent and there is not strong enough evidence on which to base a recommendation.77 1+
SMC accept the use of lidocaine plaster for patients with neuropathic pain when first-line therapies have
failed (see section 11.4).
B
Topical lidocaine should be considered for the treatment of patients with postherpetic neuralgia
if first-line pharmacological therapies have been ineffective.
5.2.7 TOPICAL RUBEFACIENTS

Topical rubefacients are more effective than topical placebo for pain reduction (NNT 6.2, 95% CI 4.0 to 13) ++
1
in patients with musculoskeletal conditions.78
B
Topical rubifacients should be considered for the treatment of pain in patients with musculoskeletal
conditions if other pharmacological therapies have been ineffective.
5.3 OPIOIDS
5.3.1 INTRODUCTION
Over the last few decades there has been a significant increase in opioid prescribing for patients with chronic
pain, despite limited evidence for long-term efficacy. There is international concern around the rise in opioid
prescribing and opioid-associated mortality rates in the United States, Australia and Europe.197-199 These
rises have been reflected in Scotland, and England.200,201 This has prompted the International Association
for the Study of Pain (IASP) to produce a statement on the use of opioids in patients with chronic pain,
which concludes that, “There may be a role for medium-term, low-dose opioid therapy in carefully selected
patients with chronic pain who can be managed in a monitored setting. However, with continuous longer-
term use, tolerance, dependence and other adaptations compromise both efficacy and safety”.202 Evidence
from the United States indicates that peri-operative opioid use may have contributed to the large increase
in prolonged opioid use.203
For the majority of clinically-used opioids, analgesic effects are predominantly, although not exclusively, via
the mu opioid receptor (MOR). The potency of different opioids at this receptor varies. Some opioids, such
as codeine, dihydrocodeine, tramadol and tapentadol, have defined upper dose limits in the British National
Formulary (BNF). The BNF classifies codeine and dihydrocodeine as ‘weak opioids’, with the other commonly-
used opioids being classed as ‘strong opioids’. Both tramadol and tapentadol have additional actions on
pain systems through noradrenergic (tapentadol) and serotoninergic reuptake inhibition (tramadol (both))
that can limit further upward titration. These additional actions on pain systems may have advantages in
some chronic pain conditions such as neuropathic or mixed pains. In 2014 tramadol was reclassified by the
UK Government as a Schedule 3 controlled drug, and recategorised by the BNF as a strong opioid (despite
its relatively low potency at MORs). Strong opioids that do not have defined upper dose limits in the BNF
include morphine, diamorphine, hydromorphone, oxycodone, fentanyl, buprenorphine and methadone.204
Some of the newer formulations (eg transdermal patch) allow very low dosing, with an equivalent effect to
less potent opioids.
Comparing doses and switching between opioids (weak or strong) should be done with caution as there is
limited evidence for the accuracy of dose equivalence tables and considerable variation between individuals
(see Annex 4 for a pathway for using strong opioids). The problems with published literature, as described in
section 1.4, remain and may contribute to an overestimation of treatment effect.
12 |
An important factor that must be considered when assessing responses to opioids is that several opioids,
including codeine, tramadol and oxycodone are affected by genetic variations in metabolism, mediated by
cytochrome P450 enzyme CYP2D6, resulting in unpredictable effects in individuals. As codeine is a prodrug
(its main effect relies on being metabolised to morphine), the 5–10% of people who are poor metabolisers
experience very little analgesia, whereas hypermetabolisers will have an increased drug effect, with increased
risk of serious adverse effects. Poor metabolisers are commonly Caucasian. Twenty-eight percent of high
metabolisers are North African or Arab, and up to 10% are Caucasian.205
In 2013 the Medicines and Healthcare products Regulating Agency (MHRA) issued guidance that breastfeeding
mothers, children under the age of 12, or children under the age of 18 who have breathing problems should
not use codeine (see https://bnf.nice.org.uk/drug/codeine-phosphate.html).
5.3.2 EFFICACY
A systematic review of 15 enriched enrolment (the exclusion of non-responders or specific inclusion of
responders) randomised withdrawal trials found short-term (<3 months) use of opioids to be effective
compared to placebo for pain reduction in patients with chronic pain. Change in pain intensity score from 1+
baseline to 12 weeks resulted in a modest effect size, SMD -0.416, 95% CI -0.521 to -0.312. Most of the trials
were in patients with chronic low back pain.206
A more recent systematic review found high-quality evidence, from 42 studies that followed up patients for
three months or longer, that opioids were associated with small but statistically significant improvements in
pain intensity compared with placebo (-0.69 cm on a 10 cm visual analogue scale, 95% CI -0.82 to -0.56 cm).207
This review also found high-quality evidence from 51 studies that opioids were associated with small but
significant improvements in physical functioning (2.04 points on the 100-point SF-36 Physical Component
Score, 95% CI, 1.41 to 2.68 points). These improvements were found to be similar to improvements in 1++
intensity and functioning obtained from other analgesics (non-steroidal anti-inflammatory drugs, tricyclic
antidepressants and antiepileptics), although these comparisons could only be based on low- to moderate-
quality evidence. Opioids were more likely than placebo to be associated with vomiting (5.9% v 2.3%, after
exclusions during the trial run-in period). The overall median follow up in all studies was 60 days (interquartile
range 30–84 days), with only two studies of duration of use up to 12 months.207
There are fewer trials of efficacy of long-term opioid use (≥3 months) in patients with chronic pain, and no
studies addressing efficacy beyond 12 months were identified.208-210 One meta-analysis included two studies 1++
of over 12 months’ duration which reported small improvements in physical health scores but not in mental 2++
health scores.210
An overview of Cochrane reviews identified no trials of high-dose opioids (≥200 mg per day morphine
equivalent dose (MED)) in patients with chronic pain, although it was unclear why the cut off of 200 mg was 1++
chosen by the authors to define high dose.211
Although there was considerable heterogeneity, four studies of oral opioids found an SMD of 1.55 (95% CI
0.85 to 2.25) in chronic non-cancer pain severity at six months, suggesting a clinically important reduction
in pain from baseline.84 There was a high drop-out rate, indicating that those who either did not benefit or
had unacceptable side effects dropped out early. Transdermal opioids showed a large reduction in pain
(SMD 7.56, 95% CI 4.65 to 10.19), although this was based on only two studies. Quality of life assessments
were limited, with no clear evidence of clinically significant benefit from either oral or transdermal opioids. 1++
There was some improvement in physical function with transdermal opioids at 12 to 13 months.84 Studies 1+
of transdermal buprenorphine at a relatively low dose (20 µg/hr) used an enriched enrolment design and
found that the 20 µg/hr preparation was effective for up to 12 weeks compared to placebo using conservative
imputation methods for missing outcome data, and also had beneficial effects on quality of life.85,86 Only one
further systematic review of trials of transdermal buprenorphine was identified since 2012: network meta-
analysis funded by the manufacturer focusing on differences in side effects compared to other therapies.212
| 13
No improvement in pain relief was found by adding short-acting opioids as rescue use medication for patients
using long-term opioids, but reported rates of nausea (25%) did not increase either.92 2++
Musculoskeletal pain
Considering specific chronic pain diagnoses, there is evidence of modest efficacy for short-term use (four to
fifteen weeks) of opioids in trials of patients with chronic low back pain.213,214 A Cochrane review reported ++
1
30% pain relief or moderate relief (odds ratio (OR) 1.91, 95% CI 1.41 to 2.58) compared to other interventions,
from studies of moderate quality.214
There was a lack of evidence for longer-term use.213 A small decrease in pain was found in moderate-quality
trials of tapentadol compared to oxycodone over twelve weeks in patients with musculoskeletal pain (0.24 ++
1
point reduction, 95% CI -0.43 to -0.05, in pain intensity from baseline in the 11-point numerical rating scale
(NRS).215 It was also better tolerated than oxycodone.215
The only longer-term RCT of opioid compared to non-opioid (eg paracetamol, NSAID) analgesia with a
primary outcome 12 months after starting treatment reported no difference in pain-related function with
opioid use up to one year compared with non-opioid medications; the non-opioid group reported a greater 1+
reduction in pain intensity (4/10 compared to 3.5/10, p<0.05).216 There was twice the prevalence of adverse
effects reported with the use of opioids than with non-opioid medication (mean 1.8 v 0.9, 95% CI 0.3 to 1.5).216
Neuropathic pain
A comprehensive systematic review of pharmacological therapies for patients with any type of neuropathic
pain reported an NNT of 4.7 (95% CI 3.6 to 6.7), to achieve at least 30% pain reduction with tramadol, and
an NNT of 4.3 (95% CI 3.4 to 5.8), for strong opioids (oxycodone or morphine).217 Numbers needed to harm
(NNH), defined by study drop outs, were 12.6 (95% CI 8.4 to 25.3) for tramadol and 11.7 (95% CI 8.4 to 19.3)
for strong opioids, although none of the trials had adverse effects as a primary outcome. When compared
with other therapies, the review provided a weak recommendation for the use of tramadol as second-line
therapy (after tricyclic antidepressants and/or gabapentinoids), and a weak recommendation for other strong ++
1
opioids as third-line therapy. There was an absence of long-term studies (beyond three months’ follow up).217
More recent Cochrane reviews of specific opioids used to treat patients with neuropathic pain also found
there were no high-quality trials. Five RCTs were identified for morphine, used for up to seven weeks, and
concluded that small study size was likely to overestimate treatment effect.218 Six RCTs of tramadol were
identified, some of which included patients with cancer pain. Small sample size and high risk of bias were
identified as issues with these RCTs.219 The remaining reviews identified three or fewer RCTs, and were unable
to draw any conclusions due to the limited evidence.220-223
5.3.3 ADVERSE EFFECTS

The clinical effectiveness of opioid therapy in any individual should be regularly assessed, with clearly defined
stopping strategies, should there be inadequate pain relief or unacceptable side effects (see Annex 4). There 1++
is a rationale for switching between opioids, if the initial choice of opioid is ineffective, and even more so if
adverse effects are unacceptable (see section 5.3.1).80
Opioids are one of the few classes of analgesics where there is not always a maximum recommended dose for
particular drugs, nor is there any agreed definition of what constitutes high-dose opioid therapy. Previously
doses of 120–200 mg have been used to define high-dose therapy, although with limited evidence.96,97 The
2++
risk of harm appears to be dose related.208,209 Updates to these definitions and other guidance, including the
4
Scottish Chronic Pain Prescribing Strategy, have all reduced the dose at which more intensive assessment
and review (a minimum of annually) are required, based at least partly on adverse effects, with many
recommending a new high limit of 90 mg, or even 50 mg.209,210,224-227
Two systematic reviews primarily examined adverse events, but these were restricted to reporting of nausea,
constipation and somnolence.92,93 Significantly less constipation was experienced with the use of tramadol
and fentanyl than other opioids.92 Patients using oxycodone experienced more somnolence than those 2++
–
2
using other opioids.92 Other commonly reported adverse events with long-term use of opioids include
gastrointestinal effects (constipation, nausea, dyspepsia), headache, fatigue, lethargy, somnolence, and
14 |
urinary complications (retention hesitancy, disturbance).84 A few serious side effects such as sedation and
respiratory depression were reported. Adverse effects led to discontinuation in 11% of patients on weak
opioids and 35–39% in strong opioids.84
No RCTs evaluating the risk of adverse effects, such as abuse or addiction, from long-term opioid therapy in ++
2
patients with chronic pain were identified; however there is evidence from observational data.209
Opioid dependence
In a systematic review, three studies from the US found that the prevalence of opioid dependence ranged
from 3% to 26% in patients who were using opioids for chronic pain.209 In two of the studies patients had a
history of dependence. Another systematic review found a wide range of estimates of the rates of misuse
of opioids used to treat patients with chronic pain, depending upon, among other things, study setting and
case definition. It concluded that rates of misuse averaged between 8% and 12%.228 A more recent systematic 2+
++
2
review, examining only prospective studies, found a pooled incidence of 4.7% of formally diagnosed 3
dependence or abuse after starting treatment with opioid analgesics; this was 0.7% in studies examining
strong opioids only.229 These findings were similar to those in an earlier systematic review which found a
median prevalence of opioid dependence syndrome of 4.5% and a median incidence of 0.5% among those
treated for pain with strong opioids.230
The use of validated tools or urine drug testing to identify patients at risk of developing opioid misuse
following analgesic prescribing (iatrogenic opioid misuse)229 has been studied. A systematic review found
weak evidence from moderate-quality studies that high scores on the Screener and Opioid Assessment for
Patients with Pain (SOAPP) Version 1 increased the likelihood for any future aberrant drug-related behaviour
(positive likelihood ratios (PLR) 2.90, 95% CI 1.91 to 4.39).96 Low scores on the SOAPP Version 1 predicted
moderately decreased likelihood of aberrant drug-related behaviours (negative likelihood ratio (NLR) 0.13,
95% CI 0.05 to 0.34). The revised SOAPP gave similar results. One poor-quality study using the Opioid Risk 2++
Tool (ORT) found that categorisation of patients as high or low risk strongly affected the likelihood of future
aberrant drug-related behaviours (PLR 14.3, 95% CI 5.35 to 38.4, and 0.08, 95% CI 0.01 to 0.62, respectively).
The Current Opioid Misuse Measure (COMM) screening tool could predict a weak increase in the likelihood
of current aberrant drug-related behaviours (PLR 2.77, 95% CI 2.06 to 3.72) with high scores and reduced
likelihood with lower scores (NLR 0.5, 95% CI 0.24 to 0.52). There was no good evidence for the use of urine
drug screening, pill counts or prescription drug monitoring programmes to detect misuse development.96
A more recent systematic review of tools for identifying problematic analgesic use found 30 studies, of low
to moderate quality, of 14 tools for detecting current, or predicting future risk of opioid misuse.231 Factors
identified as potentially increasing risk of misuse included previous history of substance misuse, deception +
2
of healthcare staff, and using other people’s medication. For identifying future risk of opioid misuse, the
Pain Medication Questionnaire and the SOAPP had the best evidence, although still of limited quality. For
identifying current misuse, the COMM was validated in three moderate-quality studies.231
Overdose
The risk of overdose may be greater for patients on higher doses of opioids. A cohort study of a small number
of patients who had experienced overdoses found a 0.2% annual risk in those on <20 mg/day morphine and
1.8% risk in those on >100 mg/day of morphine.98 Recent prescription opioid use was associated with higher ++
2
rates for any overdose event, compared to no prescribed use, (256/100,000 per annum v 36/100,000).209
This rate increased with higher doses. Compared to a baseline of ≤19 mg/day MED, the hazard ratio (HR)
for overdose with an MED of 20 to 49 mg/day was 1.44 (95% CI 0.57 to 3.62), and the HR for an MED of ≥200
mg/day was 2.88 (95% CI 1.79 to 4.63).209
Myocardial infarction
One cohort study, identified in a systematic review, of the risks of opioid therapy found that long-term use (at
least 180 days’ supply over 3.5 years) was associated with increased risk of myocardial infarction compared 2++
to no long-term opioid therapy (adjusted incidence rate ratio 2.66, 95% CI 2.30 to 3.08). Current opioid use
was also associated with an increased risk compared to using no opioids (OR 1.28, 95% CI 1.19 to 1.37).209
| 15
Endocrine harms
There is a risk of endocrine harms associated with long-term opioid use, such as erectile dysfunction and ++
2
hypogonadism.209,232,233 In women, observational studies have found a 23% to 71% occurrence of amenorrhoea 3
and decreased libido in 61% to 100% of study participants treated with opioids long term.234
Gastrointestinal side effects
Constipation is a common side effect of opioids. In a comparison of oxycodone in combination with naloxone +
1
and oxycodone with morphine, the naloxone combination had a lower incidence of constipation.235
Opioids were associated with an increased incidence of vomiting, compared to placebo, in a meta-analysis ++
1
of 33 RCTs with 1–6 months’ follow up (RR 4.12, 95% CI 3.34 to 5.07).207
Fractures
Observational studies have found current use of opioids to be associated with an increased risk of hip,
humerus, or wrist fracture compared to people not using opioids (adjusted OR 1.27, 95% CI 1.21 to 1.33). 2++
The risk was highest in patients who had recently started using opioids (OR 2.70, 95% CI 2.34 to 3.13).209
Vehicle accidents
There is evidence from a large case-control study that people taking opioids of ≥20 mg/day MED are at ++
2
greater risk of having an accident while driving compared to people on lower doses (OR 1.21 to 1.42).209
B Opioids should be considered for short- to medium-term treatment of carefully selected patients
with chronic non-malignant pain, for whom other therapies have been insufficient, and the benefits
may outweigh the risks of serious harms such as addiction, overdose and death.
99 At initiation of treatment, ensure there is agreement between prescriber and patient about expected
outcomes (see Annex 4). If these are not attained, then there should be a plan agreed in advance to
reduce and stop opioids.
99 ll patients on opioids should be assessed early after initiation, with planned reviews thereafter. These
A
should be reviewed annually, at a minimum, but more frequently if required. The aim is to achieve the
minimum effective dose and avoid harm. Treatment goals may include improvements in pain relief,
function and quality of life. Consideration should be given to a gradual early reduction to the lowest
effective dose or complete cessation.
B Currently available screening tools should not be relied upon to obtain an accurate prediction
of patients at risk of developing problem opioid use, but may have some utility as part of careful
assessment either before or during treatment.
C Signs of abuse, addiction and/or other harms should be sought at reassessment of patients using
strong opioids.
D All patients receiving opioid doses of >50 mg/day morphine equivalent should be reviewed
regularly (at least annually) to detect emerging harms and consider ongoing effectiveness. Pain
specialist advice or review should be sought at doses >90 mg/day morphine equivalent.
16 |
5.4 ANTIEPILEPSY DRUGS
5.4.1 GABAPENTIN
Using the IMMPACT definition of at least moderate benefit (at least 30% reduction in pain) gabapentin at daily
doses of at least 1,200 mg is superior to placebo for pain relief in patients with postherpetic neuralgia, painful
diabetic neuropathy or mixed neuropathic pain (NNT 6.8, 95% CI 5.6 to 8.7).99 Adverse events occurred ++
1
significantly more often with gabapentin, most commonly dizziness (21%), somnolence (16%), peripheral
oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with
placebo.
One RCT demonstrated a 30% reduction in pain over baseline, with 38/75 participants with fibromyalgia
(49%) achieving the outcome with gabapentin compared with 23/75 (31%) with placebo. The relative benefit 1++
was 1.6 (95% CI 1.1 to 2.4) and the NNT was 5.4 (95% CI 2.9 to 31).99
Gabapentin was clinically and statistically superior to placebo in reducing pain reported by patients with
chronic masticatory myalgia, masticatory muscle hyperalgesia and impact on daily functioning in a small 1+
RCT.100
A
Gabapentin (titrated up to at least 1,200 mg daily) should be considered for the treatment of patients
with neuropathic pain.
5.4.2 PREGABALIN
Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with various types of
neuropathic pain. Pregabalin at 150 mg daily was generally ineffective.101 The lowest NNT for each condition
for at least 50% pain relief over baseline for 600 mg pregabalin daily compared with placebo were 3.9 (95% ++
1
CI 3.1 to 5.1) for patients with postherpetic neuralgia, 5.0 (95% CI 4.0 to 6.6) for patients with painful diabetic
neuropathy, 5.6 (3.5 to 14) for patients with central neuropathic pain, and 11 (95% CI 7.1 to 21) for patients with
fibromyalgia.101 Higher rates of substantial benefit (≥50% pain relief) were found in patients with postherpetic
neuralgia and painful diabetic neuropathy than in patients with central neuropathic pain or fibromyalgia.101
One RCT found pregabalin to be an effective adjuvant therapy for patients with chronic pancreatitis after
three weeks of treatment, with reduction in pain reported in 36% versus 24% placebo, (95% CI 22% to 2%, 1+
p=0.02) and a higher health status, Patient’s Global Impression of Change (PGIC) score, reported in the
pregabalin group compared to placebo (44% versus 21%, p=0.048).102
With 600 mg pregabalin daily, treatment was discontinued due to adverse events in 18% to 28% of patients.101
Somnolence typically occurred in 15% to 25% of patients and dizziness occurred in 27% to 46%.101 Adverse
events related to cognition and co-ordination are commonly reported with the use of pregabalin, although 1++
none are considered to be serious, and they are dose related.103 A flexible dosing strategy (150-600 mg per 1
+
day based on clinical response and tolerability) may reduce discontinuations, facilitate a higher final dose
and give slightly greater pain relief.104
Pregabalin is not helpful in the treatment of patients with chronic prostatitis, pelvic pain or HIV neuropathy.105,106 1++
SMC restricts the use of pregabalin to adults with peripheral neuropathic pain where other first- and second-
line pharmacological treatments have failed (see section 11.4).
A pathway for patients with neuropathic pain can be found in Annex 3.
A
Pregabalin (titrated up to at least 300 mg daily) is recommended for the treatment of patients with
neuropathic pain if other first and second line pharmacological treatments have failed.
A
Pregabalin (titrated up to at least 300 mg daily) is recommended for the treatment of patients with
fibromyalgia.
B
Flexible dosing may improve tolerability. Failure to respond after an appropriate dose for several
weeks should result in trial of a different compound.
Pregabalin does not have marketing authorisation for the treatment of patients with fibromyalgia.
| 17
5.4.3 CARBAMAZEPINE
In patients with neuropathic pain carbamazepine (any dose), is significantly better than placebo over four
weeks using any definition of improvement (NNT 1.7). The trials were generally of short duration and with
some design limitations, including small sample size. Results were similar in studies reporting a 50% pain 1++
reduction over baseline. Sixty six per cent of participants using carbamazepine reported adverse events, the
most common of which was rashes.107
B
Carbamazepine should be considered for the treatment of patients with neuropathic pain. Potential
risks of adverse events should be discussed.
5.4.4 OTHER ANTIEPILEPSY DRUGS

There is little evidence from a systematic review that sodium valproate is an effective first-line treatment for
patients with chronic pain.108
A systematic review found that lacosamide is not likely to be beneficial in treating patients with neuropathic
pain.109
Lamotrigine was found to provide no benefit in the treatment of patients with chronic pain.110
1++
No evidence was found to support the use of phenytoin in the treatment of patients with neuropathic pain
or in fibromyalgia.111
There is no evidence to support the use of clonazepam in the treatment of patients with chronic neuropathic
pain or fibromyalgia.112
One RCT investigating levetiracetam did not show it to be clinically effective in the treatment of pain in
patients with polyneuropathy.113
No evidence was found on the efficacy of topiramate for the treatment of patients with chronic pain.
5.5 ANTIDEPRESSANTS
Drugs that potentiate noradrenaline and serotonin or predominantly noradrenergic mechanisms (tricyclic
antidepressants (TCA)/serotonin norepinephrine reuptake inhibitors (SNRI)), are more effective than selective 1+
serotonin reuptake inhibitors (SSRI) for treating neuropathic pain.114
There was insufficient evidence to determine the use of antidepressants in patients with temporomandibular 1++
disorders.115
99 atients with chronic pain conditions using antidepressants should be reviewed regularly and assessed
P
for ongoing need and to ensure that the benefits outweigh the risks.
5.5.1 TRICYCLIC ANTIDEPRESSANTS

There is no significant difference between tricyclic antidepressants and placebo in pain relief for patients ++
1
with chronic low back pain.60,116
Use of TCA for the treatment of patients with fibromyalgia can improve pain scores (SMD -0.43, 95% CI -0.55
to -0.30; p <0.001), depression (SMD -0.26, 95% CI, -0.39 to -0.12; p <0.001), sleep disturbances (SMD -0.32, 1++
95% CI, -0.46 to -0.18; p < 0.001) and health-related quality of life (HRQOL) (SMD -0.31, 95% CI, -0.42 to -0.20;
p <0.001).117
In patients with fibromyalgia amitriptyline was effective in reducing pain (SMD -1.64, 95% CI, -2.57 to -0.71;
p < 0.001), fatigue (SMD -1.12, 95% CI, -1.87 to -0.38; p=0.003), and sleep disturbances (weighted mean 1++
difference (WMD) -1.84, 95% CI -2.62 to -1.06; p<0.001). The effect size on depression was not statistically
significant and small in HRQOL.117
18 |
Nortriptyline combined with morphine had limited effectiveness in the treatment of patients with sciatica.118
This small RCT had a very high drop-out rate. Amitriptyline is more efficacious than placebo in relieving
neuropathic pain in patients with chronic spinal cord injury with either low- or high-grade depression.119 1+
Amitriptyline is sometimes used to treat arm pain related to repetitive use, but robust evidence of its benefit 1
++
is lacking. An RCT found that low-dose amitriptyline did not significantly decrease arm pain among these
participants but did significantly improve arm function and well-being.120
Trials of amitriptyline (25 mg to 125 mg) reporting ≥30% reduction in pain demonstrated no evidence of
effect in patients with HIV-related neuropathic pain. Analysis of combined results for patients with painful ++
1
diabetic neuropathy, postherpetic neuralgia, post-stroke pain or fibromyalgia did show benefit (RR 2.3, 95%
CI 1.8 to 3.1) compared to placebo.121 The systematic review concluded that amitriptyline is effective for a
minority of patients.
A
Tricyclic antidepressants should not be used for the management of pain in patients with chronic
low back pain.
A
Amitriptyline (25–125 mg/day) should be considered for the treatment of patients with fibromyalgia
and neuropathic pain (excluding HIV-related neuropathic pain).
99 It may be appropriate to try alternative tricyclic antidepressants to reduce the side effect profile.
5.5.2 SEROTONIN NOREPINEPHRINE RE-UPTAKE INHIBITOR

There is some evidence to support the use of duloxetine 60–120 mg in patients with chronic low back pain.
Mean changes in SF-36 bodily pain scores during treatment were 1.36 with placebo, 1.95 with duloxetine
60 mg (p<0.05 versus placebo), and 2.11 with duloxetine 120 mg (p<0.05 versus placebo). Mean changes 1
+
in RMQD-24 were -1.3 with placebo, -2.7 with duloxetine 60 mg (p<0.05 versus placebo), and -2.9 with
duloxetine 120 mg (p<0.05 versus placebo).122
Several studies and meta-analyses have shown benefit of duloxetine in patients with a variety of chronic pain
conditions. A meta-analysis of pain control in fibromyalgia has shown that treatment with duloxetine was ++
1
associated with better pain control (30% improvement in pain score, RR 1.52, 95% CI 1.24 to 1.86, p<0.0001
versus placebo; 50% improvement in pain score, RR 1.60, 95% CI 1.22 to 2.10, p=0.0007).123
Duloxetine 60 mg daily is effective in treating painful diabetic peripheral neuropathy in the short term to 12
weeks (RR for 50% pain reduction at 12 weeks 1.65 (95% CI 1.34 to 2.03), NNT 6 (95% CI 5 to 10).124 1++
Pooled data analyses from two studies in patients with knee osteoarthritis show that 64.9% of patients in the
duloxetine group, compared with 44.9% in the placebo group, reported improvement in pain from baseline to
end point (RR 1.45, 95% CI 1.22 to 1.71; p < 0.001).125 Treatment with duloxetine 60–120 mg daily is associated
with significant pain reduction and improved function in patients with pain due to osteoarthritis of the
knee.126 In this study, the Brief Pain Inventory scale (BPI) average pain response rates (≥30% pain reduction 1
+
1++
from baseline to end point) were significantly higher in the duloxetine group versus placebo group (65.3%
versus 44.1%, p≤0.001). The 50% response rates of BPI average pain did not significantly differ between the
two groups (duloxetine 43.8% versus placebo 32.3%, p=0.068).
Duloxetine was statistically superior to placebo in patients with chronic back pain on the primary endpoint
objective of reduction in average weekly pain from weeks 3–12 but lost statistical significance at the final
week.122 Duloxetine showed a statistically significant reduction in BPI average pain compared with placebo.127 1++
Duloxetine and milnacipran were effective in reducing pain by ≥50% in patients with fibromyalgia (SMD,
-0.23, 95% CI -0.29 to -0.18) compared to placebo. There were no significant improvements in quality of life,
reduction in fatigue or sleep disruption.128 1++
Rates of reported adverse effects and drop out due to adverse events did not differ between treatment and
placebo groups.117
1++
| 19
Forty per cent of patients with fibromyalgia reported ≥30% pain relief with milnacipran 100 mg or 200 mg
compared with placebo (NNT 6 to 10). Adverse effects, such as nausea and constipation, were experienced 1++
by 87% of participants treated with milnacipran compared to 78% of the placebo group.129
SMC restricts the use of duloxetine as a second- or third-line therapy for adults with diabetic peripheral
neuropathic pain (see section 11.4).
A pathway for patients with neuropathic pain can be found in Annex 3.
A
Duloxetine (60 mg/day) should be considered for the treatment of patients with diabetic
neuropathic pain if other first- or second-line pharmacological therapies have failed.
A
Duloxetine (60 mg/day) should be considered for the treatment of patients with fibromyalgia or
osteoarthritis.
Duloxetine does not have marketing authorisation for the treatment of patients with fibromyalgia or
osteoarthritis. Milnacipran is not available in the UK.
5.5.3 SELECTIVE SEROTONIN RE-UPTAKE INHIBITOR

A meta-analysis reported evidence for the efficacy of SSRIs fluoxetine (20-80 mg/day) and paroxetine (12.5-
62.5 mg/day) in reducing pain in patients with fibromyalgia (SMD -0.39, 95% CI, -0.77 to -0.01; p=0.04). 1++
Effects were small for depressed mood and HRQOL and there were no effects on fatigue or sleep. Data for
paroxetine were from a single RCT.117
B
Fluoxetine (20–80 mg/day) should be considered for the treatment of patients with fibromyalgia.
5.5.4 CHRONIC PAIN WITH CONCOMITANT DEPRESSION

An RCT of patients with chronic pain and moderate depression given optimised antidepressant therapy for
12 weeks followed by a 12 week pain self-management programme resulted in 37% of patients achieving ++
1
a ≥50% reduction in depression compared to 16% receiving usual care (RR 2.3, 95% CI 1.5 to 3.2) after 12
months. There were also moderate reductions in pain severity (≥30% reduction in pain in 51% treatment
group versus 17% usual care, RR 2.4, 95% CI 1.6 to 3.3) and disability.130
B
Optimised antidepressant therapy should be considered for the treatment of patients with chronic
pain with moderate depression.
99 epression is a common comorbidity with chronic pain. Patients should be monitored and treated
D
for depression when necessary.
5.6 COMBINATION THERAPIES

There is some evidence for combining therapies in patients with neuropathic pain, with a systematic review
identifying 21 double blind RCTs comparing combinations of at least two drugs.57 In four studies (n=578) the
combination of opioid and gabapentin or pregabalin were studied. Other combinations included opioid plus 1++
a tricyclic antidepressant (n=776), gabapentin and nortriptyline (n=56), and a variety of topical medications
(n=604). A high drop-out rate was common, with problematic side effects such as sedation and cognitive
dysfunction, which may limit the utility of combination therapies. Meta-analysis of studies of opioid plus
gabapentin (n=386) showed superiority for the combination over gabapentin alone.57
One small trial suggests that a combination of nortriptyline and gabapentin is more effective than either 1++
drug alone.57
The addition of glyceryl trinitrate (GTN) spray to sodium valproate may improve pain control in diabetes ++
1
although the evidence for valproate is poor.57
20 |
A
Combination therapies should be considered for patients with neuropathic pain (a pathway for
patients with neuropathic pain can be found in Annex 3).
A
In patients with neuropathic pain who do not respond to gabapentinoid (gabapentin/pregabalin)
alone, and who are unable to tolerate other combinations, consideration should be given to the
addition of an opioid such as morphine or oxycodone. The risks and benefits of opioid use need
to be considered.
No evidence was identified on other combinations of therapies for treating patients with chronic pain.
| 21
6 Psychologically based interventions

It has long been recognised that the perception of pain, and the disability that often arises from it, is inextricably
linked to an individual’s emotional, cognitive and social functioning.131 Living with chronic pain can also
significantly affect an individual’s mental health and, consequently, their response to treatment.132
99 ealthcare professionals referring patients for psychological assessment should attempt to assess and
H
address any concerns the patient may have about such a referral. It may be helpful to explicitly state
that the aims of psychological interventions are to increase coping skills and improve quality of life
when faced with the challenges of living with pain.
6.1 MULTIDISCIPLINARY PAIN MANAGEMENT PROGRAMMES

Multidisciplinary biopsychosocial treatment, also known as a pain management programme (PMP), addresses
the complexities experienced by patients with chronic pain.133 The definition of multidisciplinary biopsychosocial
treatment of patients with chronic pain is variable amongst studies. Three systematic reviews used the inclusion
of one physical dimension and one or more psychological, social or occupational dimensions as a minimum for
their definition.134-136 Another defined multidisciplinary treatment as including at least three of the following
categories: psychotherapy, physiotherapy, relaxation techniques, medical treatment, patient education or
vocational therapy.137 Inconsistencies in the reported results may be due to the differences in the definition
of multidisciplinary treatment, the treatment combinations, treatment intensity, setting and heterogeneity of
the study populations and control groups.
Positive results were found in a systematic review addressing non-specific musculoskeletal conditions which
grouped outcome domains into primary (pain, mood, quality of life (QoL), function and coping) and secondary
(physical capacity, return to work rate, sick leave, use of healthcare system, medication, pain behaviour, quality
of sleep and other domains (eg subjective improvement).137 An intervention was judged as successful if it
showed itself to be superior to the control condition on at least two primary outcomes or on one primary and 1++
two secondary outcomes. Thirteen of fifteen studies had positive results that multidisciplinary programmes
are superior to no treatment or standard medical treatment. The differences after treatment were maintained
in those studies which included long term follow up. Multidisciplinary treatment was also superior to other
unidisciplinary treatments (eg physiotherapy or education) in ten of the 15 studies identified. This was maintained
in follow up. Patients with low back pain or fibromyalgia had greater benefits than those with diverse origins
of chronic pain diagnoses.
Of the systematic reviews that looked at outcomes separately, two concluded that there is no demonstrable
effect that multidisciplinary treatment reduces pain for clients with non-specific chronic low back pain (CLBP)
compared to no treatment or usual care.134,136 In contrast a third systematic review found moderate evidence ++
1
that multidisciplinary treatment is superior compared to no treatment (WMD -9.47, 95% CI -13.87 to -5.87) or
other active treatments (eg physiotherapy, WMD -11.55, 95% CI -19.68 to -3.43) for reduction in short-term pain
intensity but moderate-quality evidence of no differences in long-term pain (WMD compared to no treatment
-9.27, 95% CI -27.86 to 9.12; WMD compared to active control -3.34, 95% CI -11.64 to 4.97).135
There is no demonstrable effect that multidisciplinary treatment improves functional status or disability for ++
1
patients with CLBP (WMD -8.84, 95% CI -18.49 to 0.82).134-136
One systematic review cited two high-quality studies which addressed long-term quality of life in patients who
received intensive (≥30 hours/week) multidisciplinary treatment. Only one of the studies reported significant 1
++
improvements in the multidisciplinary treatment group compared to controls.136

In patients with fibromyalgia with a risk profile for heightened psychological distress, the intervention, (described
as targeted cognitive behavioural therapy, but also including physiotherapy, therefore multidisciplinary
treatment) was found to be significantly effective in both the short- and long-term (six month follow up) in 1
++
reducing pain intensity, fatigue, disability, negative mood and quality of life, compared to a waiting list control
group.138
22 |
6 • Psychologically based interventions
One small study examined the effects of a pain management programme on outcomes for individuals with
neuropathic pain following spinal cord injury.139 Compared to waiting list controls, the intervention group
1+
experienced significant changes in two out of four secondary outcome domains not seen in the control group;
a reduction in anxiety and an increase in participation in activities. There were no significant differences in
pain intensity, pain-related disability, depression and life satisfaction.
C
Referral to a pain management programme should be considered for patients with chronic pain.
6.2 UNIDISCIPLINARY EDUCATION

Persistent pain differs from acute pain that everyone experiences occasionally. It has therefore been considered
beneficial to educate patients about these differences in order to help them understand and manage their pain
and reduce any unwarranted concerns that they may have. Educational interventions have varied in terms of
length, topics covered, the profession of those delivering them and whether or not they were combined with
other therapies.
6.2.1 BRIEF EDUCATION

Brief education for patients with CLBP is effective in reducing sick leave and disability when compared to
usual care.140 Brief education in a clinical setting (defined as "examination, information, reassurance and 1++
advice to stay active") was not shown to be any more effective at reducing pain than usual care alone.140
There is limited evidence that brief education compared to other active interventions, such as spinal
stabilisation, yoga, physiotherapy treatment, exercise, acupuncture and massage, is effective for pain or 1
++
disability in either the short or the long term. 140,141
No evidence was found on the effects of brief education on emotional outcomes, such as depression.
C
Brief education should be given to patients with chronic pain to help patients continue to work.
6.2.2 PAIN NEUROPHYSIOLOGY EDUCATION

Pain neurophysiology education (PNE) compared to a biomechanically focused education programme,
produces statistically significant but clinically small improvements in pain intensity. When PNE was added
to a pain management programme and compared to a PMP with education based on The Back Book there
was evidence that the PNE group had significantly greater reductions in pain in the short-, medium- and 1+
long-term.142,143 Although the amount of evidence is limited, PNE appears to be associated with short-term 1
++
reduction in pain intensity. Reading a book of stories and metaphors related to pain neurophysiology,
however, did not produce benefits in terms of pain reduction, but did reduce the level of catastrophising
and increased participants understanding of pain neurophysiology when this was compared to reading a
book of traditional pain management advice.144
Results are more mixed for the effects of PNE on disability with only one study finding small, short-term
effects on disability, whilst the other study that examined PNE in combination with a PMP failed to find any +
1
differences either in the short, medium or long term.142 Similarly, reading a book of metaphors and stories ++
1
relating to pain neurophysiology did not decrease disability when compared to reading a book of traditional
pain management advice.144
There is some evidence that PNE produces reliable short-term improvements in measures of attitudes towards
pain. In combination with a PMP, PNE produced greater benefits than a PMP with The Back Book education, +
1
in terms of work status at medium and long term, but not in the short term. More research is required to
improve the confidence in these results.142
| 23
6.3 BEHAVIOURAL THERAPIES
6.3.1 RESPONDENT BEHAVIOURAL THERAPIES

Respondent treatment aims to modify the physiological response system to pain, through reduction of
muscular tension. The theoretical basis of this approach is the assumption of the existence of a pain-tension
cycle, where pain is viewed as both a cause and a result of muscular tension. Respondent treatment attempts
to interrupt this cycle by using a tension-incompatible reaction, such as relaxation. Electromyographic (EMG)
biofeedback, progressive relaxation, and applied relaxation are used to reduce the assumed muscular tension,
relieve anxiety, and subsequently pain.145
There is low-quality evidence that progressive relaxation is effective for short-term pain relief compared to no
treatment and comparing pain intensity before and after treatment, in patients with chronic low back pain
1++
(WMD -19.77, 95% CI -34.34 to -5.20 and WMD -19.74, 95% CI -34.32 to -5.16).135,145 It also improved short-term
functional status and disability.135,145 Two small RCTs (n=58) suggest that progressive relaxation is not effective
for depression in the short term.145
EMG biofeedback is also effective for short-term pain relief, although this conclusion is based on low-quality
studies.135, 145 One systematic review found EMG biofeedback to be effective when disability was measured 1++
pre- and post-treatment (WMD -7.33, 95% CI -21.38 to 6.73),135 but in another, two small RCTs suggest that it
does not improve short-term functional status (SMD -0.17, 95% CI -1.56 to 1.22).145
There was no difference between progressive relaxation and cognitive therapy on post-treatment pain intensity,
disability, long-term pain or long-term disability over any length of follow up, although these conclusions are 1++
based on RCTs with a small number of participants.135,145
One systematic review identified one small RCT which found EMG biofeedback to be as effective as cognitive
behavioural therapy (CBT) post-treatment and at six month follow up for pain and behavioural outcomes.135 1++
Another small RCT found it to be more effective than progressive relaxation for short-term pain relief.145 Adding
EMG biofeedback to CBT for patients with chronic low back pain did not confer any further benefit.146
A systematic review which compared self regulatory treatments (SRTs), defined as biofeedback, relaxation and
hypnosis, to waiting list control concluded SRTs are effective at reducing post-treatment pain intensity (effect 1++
size 0.75, p<0.001) and reducing depression, immediately post treatment (effect size 0.81, p<0.05).147
Respondent therapy is as effective as CBT in improving pain relief immediately post treatment, and functional
status immediately post treatment and up to six month follow up. Results for depression were superior for 1
++
respondent therapy immediately post treatment, but there was no significant difference at six month follow up.145
C
Progressive relaxation or EMG biofeedback should be considered for the treatment of patients
with chronic pain.
6.3.2 OPERANT BEHAVIOURAL THERAPIES

Operant therapy is based on the notion that unhelpful responses can be reinforced, either by the individual’s
own behaviour, or through the behaviour of others. For example, the avoidance of pain through the avoidance
of activity is one type of natural reinforcement. Alternatively, overly concerned family, friends or healthcare
professionals may inadvertently reinforce excessive rest, with negative consequences. Operant approaches
delivered on their own are uncommon in Scotland but frequently form part of multidisciplinary rehabilitation
programmes that are based on cognitive behavioural principles.
Two systematic reviews of patients with chronic low back pain identified RCTs of varying size and quality.135,145
Compared to waiting list controls, pain intensity was reduced post treatment following an operant behavioural 1++
therapy intervention (SMD -0.43, 95% CI -0.75 to -0.11, and WMD -7.00, 95% CI -12.33 to-1.67). There was no
evidence of short-term improvement in functional outcomes.
Evidence on the effect of operant behavioural therapy on mood is mixed. One review combined outcomes ++
1
from two RCTs (described as low quality) and found no significant difference between operant therapy and
24 |
6 • Psychologically based interventions
waiting list controls on depressive symptoms in the short term.145 A second systematic review identified one
study, with a low risk of bias, which found a significant reduction in negative effect immediately post treatment 1++
that favoured the operant therapy group.135
Both reviews suggest that combining operant therapy with exercise confers no reliable benefit over exercise ++
1
therapy alone for reduction in pain intensity, depression and improved functional status.135, 145
Evidence of moderate quality showed no significant difference in pain intensity between patients receiving
operant therapy compared to those receiving cognitive therapy in the short to medium term. There was no 1++
significant difference between operant therapy and combined behavioural treatments for improved pain
relief in the short, medium or long term.145
99 linicians should be aware of the possibility that their own behaviour, and the clinical environment,
C
can impact on reinforcement of unhelpful responses.
6.4 COGNITIVE BEHAVIOURAL THERAPY

Although many PMPs are based on cognitive behavioural principles, CBT can also be delivered as a unidisciplinary
intervention, facilitated by appropriately qualified staff.
A systematic review found no short-term benefit of CBT compared to usual care in patients with orofacial
pain, but at three month follow up there was significant improvement in pain reduction, depression, activity 1++
interference and disability.148
Adding cognitive behavioural principles to exercises for chronic neck pain within unidisciplinary physiotherapy
treatment yielded no additional benefit in terms of disability. Similarly there were no differences between 1+
groups in terms of numerical pain ratings, quality of life, patients’ ratings of treatment efficacy or patients’
satisfaction with the treatment.149
In patients with CLBP CBT is effective in reducing pain intensity immediately post treatment compared to ++
1
waiting list controls. There was no difference in depression or health-related quality of life.147
Compared to waiting list controls, CBT and CBT combined with biofeedback in patients with chronic back pain
both showed benefit in:146
yy r educing pain intensity, CBT; effect size 0.47 (95% CI 0.19 to 0.7), CBT plus biofeedback; 0.67 (95% CI 0.39
to 0.95)
yy reducing consumption of analgesic medicines, CBT; effect size 0.46 (95% CI 0.18 to 0.74), CBT plus
biofeedback; 0.31 (95% CI 0.06 to 0.56)
yy reducing pain-related disability, CBT; effect size 0.38 (95% CI 0.10 to 0.66), CBT plus biofeedback; 0.44 1++
(95% CI 0.18 to 0.70)
yy improvement in health-related quality of life, CBT; effect size 0.47 (95% CI 0.19 to 0.75), CBT plus
biofeedback; 0.39 (95% CI 0.13 to 0.65)
yy improvement in adaptive coping strategies, CBT; effect size 0.82 (95% CI 0.51 to 1.13), CBT plus biofeedback;
0.61 (95% CI 0.34 to 0.88)
yy reducing depression, CBT; effect size 0.29 (95% CI 0.02 to 0.56), CBT plus biofeedback; 0.35 (95% CI 0.09
to 0.61)
yy reducing the number of doctor visits, CBT; effect size 0.33 (95% CI 0.06 to 0.60), CBT plus biofeedback;
0.38 (95% CI 0.12 to 0.64).
These results were maintained at six month follow up with the exception of depression and number of doctor
visits in the CBT group and consumption of analgesic medicines in the combined therapies group.
One small study of individuals with rheumatoid arthritis compared behavioural therapy (BT) to cognitive
therapy (CT) and to CBT.150 Although this study had a small number of participants, where there were
differences, these tended to favour therapies with a cognitive component. Improvements were noted in 1
+
C-reactive protein immediately post treatment and tender joint count. Similar improvements were found in
the CT and CBT groups at six month follow up. Anxiety was improved in the CT and BT groups, post treatment,
but not in the CBT and waiting list group.
| 25
Significant improvements in self-rated global health were found after telephone-delivered CBT compared to
usual care in patients with widespread chronic pain, at six- and nine-month follow up.151 At six months sleep
had also improved for patients receiving telephone CBT. Combining telephone CBT with exercise brought a
wider range of benefits at six-month follow up compared to usual care including self-rated global health, 1++
fatigue, self-rated physical health, and active and passive pain coping, but this combined treatment was no
better than usual care when it came to sleep, self-rated mental health, combination measure of pain and
functioning and emotional well-being. These differences were maintained in only two measures (self-rated
global health and passive pain coping) at nine-month follow up.
A small RCT of internet-based CBT showed improvements in the quality of life and pain catastrophising subscale +
1
on the pain coping measure at 12 weeks. Other outcomes were not significantly different to the control group.152
Compared to education alone, CBT appears to be more effective in improving depression and pain
catastrophising, in patients with chronic pain, although this result was not statistically significant after intention- 1+
to-treat analysis.153
C
Cognitive behavioural therapy should be considered for the treatment of patients with chronic
pain.
6.5 MINDFULNESS MEDITATION AND ACCEPTANCE AND COMMITMENT THERAPY

Mindfulness meditation has become an increasingly popular intervention for chronic pain and other long
term conditions. Through encouraging participants to pay attention in a particular way, it is thought to foster
a greater willingness to accept what are sometimes aversive experiences. Mindfulness meditation is often
delivered as part of a manualised educational package. The most commonly-used package is mindfulness-
based stress reduction (MBSR). This is a structured programme that combines various meditation practices
with modified yoga exercises and mind-body education.
Like mindfulness meditation, acceptance and commitment therapy (ACT) encourages participants to re-
evaluate their relationship with their experiences, including learning to develop a greater distinction between
themselves and their thoughts. These changes are used to help individuals to become more psychologically
flexible. In essence, ACT changes the agenda away from controlling aversive experiences and instead facilitates
a focus on setting values-based goals.
A systematic review of mixed study types found that less well-controlled studies showed larger effects and
significant improvements from the use of MBSR across outcome measures: pain (SMD 0.48, 95% CI 0.25 to
0.71), depression (SMD 0.50, 95% CI 0.12 to 0.89), anxiety, physical well-being and quality of life.154 Results from
the randomised controlled trials showed small but significant improvements in pain (SMD 0.25, 95% CI 0.01
to 0.49) and depression (SMD 0.26, 95% CI 0.05 to 0.47) and small to moderate improvements in measures of 2++
physical well-being. No significant improvements were found in anxiety or quality of life. The authors found 1
++
some evidence of a publication bias when depression was used as an outcome measure which suggested that
small studies that found negative results were not being published.154 Some of the studies included may have
been underpowered as sample sizes were small. Two further RCTs concluded that MBSR provided no benefit
compared to controls or an educational programme.155,156
A review of trials of mindfulness-based interventions (MBI), which included MBSR in six of the 10 trials, showed
that MBI produced superior results in terms of pain control when compared with an educational control group 2+
and a control group who received massage. CBT was, however, better at reducing pain than MBI.157
Comparisons between patients on an ACT-based programme and a CBT programme showed no significant
differences in terms of pain intensity, pain interference, depression, pain-related anxiety, general activity on
the Multidimensional Pain Inventory (MPI), and mental- and physical-related quality of life rating on the SF-12 1++
scale. The within-groups analysis showed significant improvements in both the ACT and CBT groups following
treatment in terms of pain interference, depression, and pain-related anxiety, but not in pain severity, the MPI
or the SF-12 subscales compared to treatment as usual.158

26 |
7 • Physical therapies
7 Physical therapies
7.1 MANUAL THERAPY
7.1.1 LOW BACK PAIN

Manual therapy (MT) is an umbrella term that has increasingly been adopted to encompass various forms
of hands-on treatment, including both manipulation and mobilisation.
Mobilisation techniques involve the therapist applying slow, passive movements to a joint; typically the
patient cannot perform these movements independently but they are within the normal physiological range
of motion of the joint. Manipulation is a passive technique where the therapist applies a specifically directed
manual thrust to a joint, at or near the end of the physiological range of motion. This may be accompanied
by an audible ‘crack’ or ‘pop’.
Manual therapy as a treatment option in the management of pain is an intervention that is practised by a
variety of healthcare professionals including physiotherapists, osteopaths and chiropractors. Philosophical
differences exist both within and between the various professions regarding the possible mechanisms of
action of manual therapy.
Whilst there is extensive, although generally poor quality, literature with regards to the effectiveness of
various MT approaches these are usually compared to placebo. There are few head-to-head trials of different
approaches.
For the purpose of the guideline studies were included if they encompassed an intervention that could be
described as including a manual therapy treatment arm.
A Cochrane review found high-quality evidence that spinal manipulation therapy (SMT) is as effective as other
interventions, in the short term, for pain relief (SMD -4.16, 95% CI -6.97 to -1.36) and functional status (SMD 1++
-0.22, 95% CI -0.36 to -0.07) for patients with chronic low back pain.159 It was not found to be significantly
more effective than sham or inert interventions, although these studies were of poor quality.159
A mixture of RCTs of varying quality show that SMT has a statistically significant, short-term difference on ++
1
pain relief and functional status when combined with another intervention.159
Evidence from poor-quality studies show that there is no statistically significant difference in effect on pain ++
1
intensity and disability, from exercise compared to manual therapy at short- and long-term follow up.135
Massage provides short-term pain relief for patients with chronic low back pain, although this conclusion ++
1
is based on studies of low quality.160
B
Manual therapy should be considered for short-term relief of pain for patients with chronic low
back pain.
7.1.2 NECK PAIN

Manual therapy combined with exercise demonstrated long-term improvements in pain (pooled SMD -0.87,
95% CI -1.69 to -0.06), function/disability, and global perceived effect compared to no treatment in patients
with neck pain, although this conclusion is based on low-quality studies.161 The same systematic review
identified better quality evidence which demonstrated that manual therapy and exercise provides greater 1
++
short-term relief compared with exercise alone (pooled SMD -0.50, 95% CI -0.76 to -0.24). There were no
long-term differences across multiple outcomes.161 Combined therapy resulted in greater pain reduction
and improved quality of life compared to manual therapy alone (pooled SMD -0.31, 95% CI -0.61 to -0.02);
heterogeneity: p=0.04, I2=0%).161
Manual therapy may provide short-term relief compared with control (pooled SMD -0.90, 95% CI -1.78 to
-0.02).162 Nine or 12 sessions were superior to three for reduction in pain, disability and cervicogenic headache. 1++
These results are based on low-quality studies.162
| 27
Low-quality evidence supported a single session of thoracic manipulation for immediate pain reduction ++
1
compared to placebo for patients with chronic neck pain (NNT 5, 29% treatment advantage).162
B
Manual therapy, in combination with exercise, should be considered for the treatment of patients
with chronic neck pain.
7.2 EXERCISE
Evidence identified on exercise as a treatment intervention for patients with chronic pain revealed
heterogeneous studies, and a relatively small number of good-quality systematic reviews. A lack of clear
definition of the exact format of exercise interventions made direct comparison difficult. Recommendations
can be made relating to exercise approaches and the format of delivery.
7.2.1 EXERCISE APPROACH

Aerobic and strength conditioning exercises
In patients with fibromyalgia aerobic-only exercise training at the recommended intensity levels had positive
effects on global well-being (SMD 0.49, 95% CI 0.23 to 0.75) and physical function (SMD 0.66, 95% CI 0.41 to 1++
0.92) and possibly on pain (SMD 0.65, 95% CI -0.09 to 1.39) and tender points (SMD 0.23, 95% CI -0.18 to 0.65).
Supervised aerobic exercise training was also found to have some benefits on fibromyalgia symptoms.163
Movement facilitation and stabilisation exercises
Unloaded movement facilitation exercise compared to no exercise is effective for improving pain and
function in patients with non-specific chronic low back pain. Compared to other types of exercise, including
effort-intensive trunk strengthening and time-intensive specific stabilisation, the effects are comparable. 1
++
For many people with non-specific chronic low back pain, unloaded exercise is as helpful as quite vigorous
exercise against resistance.164
High-quality trials support the use of stabilisation exercises in patients with chronic back pain. Overall the
evidence was conflicting and significant differences favouring stabilisation exercises were less likely when 1++
they were compared with active treatment control groups rather than inactive control groups.165
Walking
A systematic review identified moderate evidence that walking alone does not have a positive effect in the
management of patients with low back pain compared with individual-based exercise. Additionally there 2+
was poor-quality evidence for treadmill walking as an effective management strategy.166
T’ai Chi, pilates and yoga
Pooled data from poor-quality studies showed T’ai Chi has a small positive effect for reducing pain and
1++
improving disability in people with chronic arthritis. The duration of these effects was not reported.167
Pilates was superior to minimal intervention for reduction of pain in individuals with persistent non-specific
low back pain, but no more effective than other forms of exercise to reduce pain. In this instance the pilates 1++
component of the exercises that were used was not defined.168
Yoga can be a useful supplementary approach to treatment with moderate effect sizes on pain and associated +
1
disability. The yoga interventions used in and between trials included in the meta-analysis were not defined.169
Therapeutic aquatic exercise
Therapeutic aquatic exercise may be beneficial for patients with chronic low back pain.170 1+
Exercise therapy
A systematic review on the effectiveness of physical and rehabilitation interventions for patients with chronic
non-specific low back pain of more than 12 weeks duration comparing exercise therapy with usual care and 1++
advice to stay active showed a significant decrease in pain intensity and disability in favour of the exercise
therapy.135
28 |
7 • Physical therapies
Statistical pooling of three studies showed a significant decrease in pain intensity and disability in favour of
the exercise group (WMD -9.23, 95% CI -16.02 to -2.43 and -12.35, 95% CI -23.00 to -1.69, respectively). One
study found a statistically significant difference at intermediate (five-month) follow up in pain relief for the 1++
exercise group compared to the usual care group. Three studies reported on pain and/or disability at long-term
follow up. The pooled WMD for pain was not statistically significant (-4.94, 95% CI -10.45 to 0.58); the WMD
for disability was statistically significant in favour of the exercise group (WMD -3.17, 95% CI -5.96 to -0.38).135
No difference in pain reduction and disability was found in short-term results of poor-quality studies
comparing exercise therapy with waiting list controls, but there was some evidence that it improved pain 1++
intensity and disability compared to usual care.135
7.2.2 ADVICE
The addition of interventions based on CBT to physiotherapy programmes may be effective for people with ++
1
whiplash-associated disorder.171
A systematic review of advice for the management of chronic low back pain found strong evidence to
suggest that advice as an adjunct to exercise was more effective for improving pain, back specific function 1++
and work disability as opposed to advice alone. Advice in this sense was to stay active, along with specific
advice regarding exercise and/or functional activities.50
7.2.3 EXERCISE DELIVERY

Supervised exercise was found to be more effective for improving weekly training frequency than
unsupervised exercise. Supplementing a home exercise programme with group exercise may increase overall 1
++
physical activity levels.171

Performance accuracy is improved by refresher sessions or by providing audiotapes or videotapes of 1++
exercises.171
A systematic review of therapeutic interventions for patients with whiplash-associated disorder, including
chronic whiplash of more than 12 weeks duration, indicated that an exercise programme was effective in 2+
relieving chronic whiplash-related pain in the short term although these gains were not maintained in the
long term. The relative effectiveness of different exercise regimens was not determined.172
7.2.4 HETEROGENEITY OF EXERCISE

One study identified on the effect of exercise on pain and disability in patients with CLBP aimed to explain
between-trial heterogeneity.173 When all types of exercise were analysed, small but significant reductions ++
1
in pain and disability were observed compared with minimal care or no treatment. Despite many possible
sources of heterogeneity in exercise trials, only the dosage (intensity, duration, amount) was significantly
associated with effect sizes.
7.2.5 EXERCISE ADHERENCE

A Cochrane review considering adherence to exercise in patients with chronic musculoskeletal conditions
identified moderate-quality evidence that:171
yy Individual-specific exercises are more effective than generic group exercise for improving attendance
at exercise classes. 1++
yy Therapeutic programmes that specifically address adherence are effective in improving the frequency/
duration of exercise, and attendance at sessions.
yy Graded activity is effective in improving adherence to a home exercise programme.
yy Adding CBT-based approaches to physiotherapy programmes is not effective in improving exercise
adherence.
B
Exercise and exercise therapies, regardless of their form, are recommended in the management
| 29
A
Advice to stay active should be given in addition to exercise therapy for patients with chronic low
back pain to improve disability in the long term. Advice alone is insufficient.
B The following approaches should be used to improve adherence to exercise:

yy supervised exercise sessions
yy individualised exercises in group settings
yy addition of supplementary material
yy provision of a combined group and home exercise programme.
7.3 TRACTION
There is strong evidence that there is no statistically significant difference in outcome between traction as
a single treatment against placebo, sham or no treatment for patients with acute, subacute or chronic low 1++
back pain with and without sciatica. The addition of continuous traction to standard physiotherapy practice
did not affect outcomes either.174
Conflicting evidence was found when comparing autotraction with placebo, sham or no treatment; other ++
1
forms of traction with other forms of treatment and different forms of traction compared to each other.174
7.4 ELECTROTHERAPY
Active transcutaneous electrical nerve stimulation (TENS) treatments have shown a positive analgesic ++
1
outcome in patients with chronic pain. Little difference was found between high and low frequencies.175
There is conflicting evidence about whether the use of TENS for chronic low back pain is beneficial in reducing 1+
pain intensity, but consistent evidence from two studies showed that it did not improve functional status.176,177 1++
There is low-quality evidence that pulsed electromagnetic field therapy, repetitive magnetic stimulation ++
1
and transcutaneous electrical nerve stimulation are more effective than placebo in reducing neck pain.178
The use of TENS in patients with peripheral diabetic neuropathy reduces pain intensity.176 1+
Studies of low-level laser therapy (LLLT) have shown statistically significant but clinically unimportant pain
relief compared to sham therapy for patients with sub-acute and chronic low back pain at short-term and
intermediate-term follow up (up to six months).179 In one study LLLT was more effective than sham at reducing 1
++
disability in the short term. LLLT or the addition of LLLT to exercise was not better than exercise alone, with
or without sham in reducing pain or disability in the short term.179
The relapse rate in the LLLT group was significantly lower than in the control group at the six-month follow ++
1
up. No side effects were reported.179
B
Transcutaneous electrical nerve stimulation should be considered for the relief of chronic pain.
Either low or high frequency TENS can be used.
B
Low-level laser therapy should be considered as a treatment option for patients with chronic low
back pain.
30 |
8 • Complementary therapies
8 Complementary therapies
8.1 ACUPUNCTURE
Systematic reviews have identified RCTs of varying quality which show a small clinically relevant benefit from
acupuncture for short-term pain relief for patients with chronic knee pain, compared to sham and chronic
low back pain versus waiting list control or when added to another intervention.180,181 At six to twelve months 1+
++
1
follow-up patients with knee pain were still reporting significant improvements in pain reduction, while
results were inconsistent for those with back pain.
Meta-analysis of acupuncture versus no acupuncture studies (with various end points) showed overall benefit
of acupuncture for pain relief and functional status in patients with back and neck pain (SD 0.55, 95% CI 0.51 1++
to 0.58) and osteoarthritis (SD 0.57, 95% CI 0.50 to 0.64).182
For patients with osteoarthritis pain, acupuncture showed improvement in pain relief compared to sham at
short-term (SMD -0.28, 95% CI -0.45 to -0.11), and at six-month follow up (SMD -0.10, 95% CI -0.21 to 0.01).
Compared to waiting list controls acupuncture demonstrated a clinically significant improvement in short- 1++
term pain relief (SMD -0.96, 95% CI -1.19 to -0.72).183 An additional RCT of patients with osteoarthritis of the 1
+
knee or hip reported a significant difference at three months between acupuncture and routine care, (SF-36
bodily pain scores SD 50.7 ±23.5 compared to SD 36.3 ±18.3).184
Many studies used sham acupuncture, which may have a physiological effect, as a control which may result ++
1
in smaller effect sizes.183
A systematic review of acupuncture for patients with chronic non-bacterial prostatitis/chronic pelvic pain
syndrome identified nine RCTs which suggested that acupuncture is effective as part of a multi-interventional 1++
approach. The findings are based on poor-quality trials.185
Meta-analysis of five studies showed auricular acupuncture can be an effective treatment for various types
of pain or as an adjunct to other therapies (compared to sham, placebo or usual care, overall change in pain 1++
score SMD 1.84, 95% CI 0.60 to 3.07).186
No benefit was found for patients with rheumatoid arthritis, and there was insufficient evidence to support ++
1
the use of acupuncture in patients with fibromyalgia.187
1+
Acupuncture delivered by qualified practitioners is not associated with serious adverse events.182, 183, 187
1++
A
Acupuncture should be considered for short-term relief of pain in patients with chronic low back
pain or osteoarthritis.
8.2 HERBAL MEDICINE

A systematic review of the use of herbal medicines in patients with chronic low back pain found few studies and
those identified were small and of low quality. Two small RCTs found willow bark (salic alba) to have significant
1++
short-term effects on pain relief but not recovery.181 In patients with osteoarthritis it was not found to be more
effective than placebo in one trial, while in another, 14% of patients reported reduction in pain compared to
2% on placebo.188
Limited evidence has shown the following interventions to be effective for patients with osteoarthritis.188
yy Four small RCTs reported improvement in pain with Indian frankincense.
yy Ginger was reported as being more effective than placebo, but not as effective as ibuprofen in three RCTs 1+
of short-term and up to six months’ duration.
yy Three studies found devil’s claw to improve osteoarthritis-related symptoms to similar levels to conventional
therapies. There is a risk of side effects and interaction with anticoagulants, NSAIDs, cardiovascular and
gastric acid drugs.
Two studies showed no benefit in the use of harpagophytum over placebo.181 1++
| 31
No good-quality studies were identified in a Cochrane review of Chinese herbal medicine for patients with
1++
chronic neck pain.189
8.3 OTHER THERAPIES

A Cochrane review of music therapy for all types of pain identified three studies of adults with chronic pain. ++
1
The trials were small, of poor quality and reported inconsistent results.190
Two RCTs of aromatherapy in patients with fibromyalgia showed no difference in efficacy between the treatment ++
1
and control groups.187
Results from trials of homeopathy in patients with rheumatoid arthritis, osteoarthritis and fibromyalgia were 1++
inconsistent.187
One RCT of patients with low back pain found no significant difference between those who received reflexology ++
1
and those who received group-based relaxation or usual care.187
No good-quality studies were identified to evaluate the efficacy of hypnotherapy or reiki.
32 |
9 • Dietary therapies
9 Dietary therapies
Few good-quality RCTs are available on diet supplementation to treat patients with chronic pain symptoms.191 4
A Cochrane review looking at the impact of various types of diet, such as vegetarian, Mediterranean, and
elimination diets, on pain and functional status in patients with rheumatoid arthritis concluded that the 1++
studies identified were too small and not of sufficient quality to determine efficacy.192
A Cochrane review of vitamin D supplementation for patients with chronic pain identified four studies. Only
one of the studies reported a benefit in terms of reduction in analgesics used, but was considered to be 1++
methodologically poor.193
Dietary interventions were most effective when combined with deep breathing techniques and acupuncture.
The naturopathic approach was linked to improved quality of life, reduced body mass index and reduced back 1
+
pain (-6.89, 95% CI -9.23 to -3.54, p <0.0001) when compared to physiotherapy.194

Omega-3 fatty acid taken as a fish oil is effective in reducing joint pain.188 1+
Green lipped mussel extract was no better than placebo in patients with rheumatoid arthritis.188 1+
Limited evidence has shown the following interventions to be effective for patients with osteoarthritis:188
yy S -adenosylmethionine (SAMe). A systematic review and two RCTs reported that SAMe (400 mg, 600 mg or
1,200 mg per day) had similar effects on pain reduction and functional ability as treatment with NSAIDs for +
1
up to 12 weeks duration (effect size for pain 0.12; 95% CI, -0.029 to 0.273).
yy Bioflavinoids (pine bark extracts). One RCT (n=156) reported a reduction in pain in 56% of the treatment
group compared to 10% in the placebo group.
yy Rosehip. A systematic review found trials reporting that 5 g of rosehip showed a reduction in pain and in
painkiller use compared to placebo.
| 33
10 Provision of information
This section reflects the issues likely to be of most concern to patients and their carers. These points are provided
for use by health professionals when discussing chronic pain with patients and carers and in guiding the
production of locally produced information materials.
10.1 SOURCES OF FURTHER INFORMATION

British Complementary Medicine Association
P.O. Box 5122, Bournemouth, BH8 0WG
Tel: 0845 345 5977
www.bcma.co.uk
A professional umbrella organisation which provides a ‘find a therapist’ service.
British Pain Society
Third Floor, Churchill House, 35 Red Lion Square, London WC1R 4SG
Tel: 020 7269 7840
www.britishpainsociety.org  Email: [email protected]
A multidisciplinary professional organisation which aims to promote education, training, research and
development in all fields of pain. It endeavours to increase both professional and public awareness of the
prevalence of pain and the facilities that are available for its management. Provides pathways for patient
care. The website includes a list of UK based organisations that specialise in helping patients with specific
underlying conditions that cause chronic pain.
Chronic Pain Policy Coalition
Policy Connect, CAN Mezzanine, 32–36 Loman Street, Southwark, London, SE1 0EH
Tel: 020 7202 8580
www.policyconnect.org.uk/cppc  E-mail: [email protected]
A forum to unite patients, professionals and parliamentarians in a mission to develop an improved strategy
for the prevention, treatment and management of chronic pain and its associated conditions.
Health and Social Care Alliance Scotland
Venlaw Building, 349 Bath Street, Glasgow, G2 4AA
Tel: 0141 404 0231  Fax: 0141 246 0348
www.alliance-scotland.org.uk  E-mail: [email protected]
The national third sector health and social care intermediary. It brings together over 270 organisations to
ensure the voice of people and unpaid carers, and the expertise of the third sector, are influential in shaping
policy and practice.
Healthtalkonline Database
www.healthtalkonline.org
An online database of patient’s experiences and information on around 50 health conditions.
National Chronic Pain Website for Scotland
www.chronicpainscotland.org
A website which provides information, advice, education and resources for people with pain, for families
and carers as well as for healthcare professionals and Service Improvement Groups. It provides details of
specialist pain management services in Scottish NHS Boards and voluntary organisations.
NHS Inform
www.nhsinform.co.uk
The national health information service.
34 |
10 • Provision of information
Pain Association Scotland

Suite D, Moncrieffe Business Centre, Friarton Road, Perth, PH2 8DG
Tel: 0800 783 6059
www.painassociation.com  Email: [email protected]
An organisation which develops and delivers self management training for people with chronic pain,
addressing the non-medical issues, particularly the disabling effects of chronic pain which impact on people’s
lives. The focus is to introduce people to, and quickly build self-management skills, thereby creating practical,
positive change leading to an improved quality of life and well-being.
Pain Concern
Unit 1-3, 62-66 Newcraighall Road, Fort Kinnaird, Edinburgh, EH15 3HS
Tel: 0131 669 5951  Helpline: 0300 123 0789
www.painconcern.org.uk  Email: [email protected]
Facebook facebook.com/painconcern  Twitter @PainConcern
Pain Concern provides information and support to people with pain and their carers and aims to raise
awareness about pain and improve the provision of pain management services. Their Airing Pain radio
show is a series of audio podcasts featuring the experiences of those managing their everyday pain and
interviews with top, internationally recognised experts. Their magazine Pain Matters contains news, features
and comment on topics including self-management techniques, research into pain treatments and personal
experiences of living with pain. They run a helpline and an online community on HealthUnlocked which
provides members with a forum to share experiences.
Pain Support
www.painsupport.co.uk
Pain Support provides pain relief techniques for those with chronic pain. There is also a regular email
newsletter, a discussion forum and a contact club for making new friends, plus a shop for books,
relaxation CDs and downloads.
Pain UK
www.painuk.org
Pain UK aims to bring together pain charities in the UK to speak up about the common needs of the people
they represent. It aims to provide training and support to member charities, signpost support for people
living with pain and raise awareness for new forms of support, when needed.
10.1.1 SELF MANAGEMENT TOOLS

Arthritis Care
www.arthritiscare.org.uk/LivingwithArthritis/Self-management
Centers for Disease Control and Prevention
www.cdc.gov/arthritis/interventions/self_manage.htm
Expert Patient Programme
www.nhs.uk/NHSEngland/AboutNHSservices/doctors/Pages/expert-patients-programme.aspx
Pain Association Scotland
www.painassociation.com
Pain Tool Kit
www.paintoolkit.org
| 35
10.2 CHECKLIST FOR PROVISION OF INFORMATION

This section gives examples of the information patients/carers may find helpful at the key stages of the
patient journey. The checklist was designed by members of the guideline development group based on their
experience and their understanding of the evidence base. The checklist is neither exhaustive nor exclusive.
Patient pathways can be found in Annexes 2 to 4.
Assessment
yy Explain the mechanism of pain and the benefits of a holistic approach to managing the pain.
yy E ncourage the patient to return within an agreed timescale if the initial planned treatment/s are not
having the desired effect, and explain that there are other treatments that may be more effective.
yy Provide information on self management and where to access resources suitable to the individual.
yy Give advice on exercise and encouragement to stay active.
Pharmacological management
yy G
ive advice on the treatment being given, the reasoning behind the treatment, the potential side
effects and periodically review the medicines prescribed.
Psychological therapies
yy E nsure the patient is aware that pain management programmes are a group-based treatment to
improve quality of life.
Complementary therapies
yy A
dvise patients seeking therapies outwith the NHS to ensure the practitioner is a member of the
appropriate professional regulatory body.
yy A
dvise patients to inform their GP/healthcare professional of any complementary therapies or
supplements they may be taking.
36 |
11 • Implementing the guideline
11 Implementing the guideline

This section provides advice on the resource implications associated with implementing the key clinical
recommendations, and advice on audit as a tool to aid implementation.
11.1 IMPLEMENTATION STRATEGY

Implementation of national clinical guidelines is the responsibility of each NHS board and is an essential
part of clinical governance. Mechanisms should be in place to review care provided against the guideline
recommendations. The reasons for any differences should be assessed and addressed where appropriate.
Local arrangements should then be made to implement the national guideline in individual hospitals, units
and practices.
Implementation of this guideline will be encouraged by SIGN and actively supported by the Chronic Pain
Service Improvement Groups. The Scottish Government is supporting NHS boards to establish local Service
Improvement Groups in a two year development programme that aims to implement the Scottish service
model for chronic pain across Scotland (see Annex 5).
11.2 RESOURCE IMPLICATIONS OF KEY RECOMMENDATIONS

No recommendations were identified as having significant budgetary impact.
11.3 AUDITING CURRENT PRACTICE

A first step in implementing a clinical practice guideline is to gain an understanding of current clinical
practice. Audit tools designed around guideline recommendations can assist in this process. Audit tools
should be comprehensive but not time consuming to use. Successful implementation and audit of guideline
recommendations requires good communication between staff and multidisciplinary team working.
The guideline development group has identified the following as key points to audit to assist with the
implementation of this guideline:
yy the number of patients presenting with chronic pain
yy the number of patients using analgesics to manage chronic pain who receive an annual review
yy the number of patients on opioids and gabapentinoids who receive an annual review of their medications
yy the number of patients on >180 mg/day morphine or equivalent referred for specialist assessment
yy the number of patients referred for self management.
A core national dataset for audit for chronic pain services in Scotland is also available at
www.chronicpainscotland.org.
| 37
11.4 ADDITIONAL ADVICE TO NHSSCOTLAND FROM HEALTHCARE IMPROVEMENT SCOTLAND

AND THE SCOTTISH MEDICINES CONSORTIUM
yy C apsaicin cutaneous patch is accepted for restricted use by the Scottish Medicines Consortium for the
treatment of adults with postherpetic neuralgia who have not achieved adequate pain relief from, or
who have not tolerated, conventional first- and second-line treatments. Treatment should be under the
supervision of a specialist in pain management (February 2011).
yy Lidocaine 5% medicated plaster is accepted for restricted use within NHSScotland for the treatment of
patients with neuropathic pain associated with previous herpes zoster infection (postherpetic neuralgia). It
is restricted to use in patients who are intolerant of first-line systemic therapies for postherpetic neuralgia
or where these therapies have been ineffective (August 2008).
yy Pregabalin is accepted for restricted use within NHSScotland for the treatment of peripheral neuropathic
pain in adults who have not achieved adequate pain relief from, or have not tolerated, conventional first-
and second-line treatments for peripheral neuropathic pain. Treatment should be stopped if the patient
has not shown sufficient benefit within eight weeks of reaching the maximally tolerated therapeutic
dose (May 2009). Pregabalin oral solution should be prescribed only for patients who find it difficult to,
or are unable, to swallow tablets (June 2012).
yy Duloxetine 30 mg and 60 mg is accepted for restricted use for the treatment of diabetic peripheral
neuropathic pain in adults (September 2006). Duloxetine is restricted to initiation by prescribers
experienced in the management of diabetic peripheral neuropathic pain as second- or third-line therapy.
38 |
12 • The evidence base
12 The evidence base

12.1 SYSTEMATIC LITERATURE REVIEW
The evidence base for this guideline was synthesised in accordance with SIGN methodology. A systematic review
of the literature was carried out using an explicit search strategy devised by a SIGN Evidence and Information
Scientist. Databases searched include Medline, Embase, Cinahl, PsycINFO and the Cochrane Library. The year
range covered was 2007-2012. Internet searches were carried out on various websites including the US National
Guidelines Clearinghouse. The main searches were supplemented by material identified by individual members
of the development group. Each of the selected papers was evaluated by two members of the group using
standard SIGN methodological checklists before conclusions were considered as evidence.
In 2018 a systematic review of the literature for the efficacy and safety of opioids in patients with chronic pain
was conducted following the protocols described above. The databases Medline, Embase and the Cochrane
Library were searched for the year range 2014–2018.
12.1.1 LITERATURE SEARCH FOR PATIENT ISSUES

At the start of the guideline development process, a SIGN Evidence and Information Scientist conducted
a literature search for qualitative and quantitative studies that addressed patient issues of relevance to
management of patients with chronic pain. Databases searched include Medline, Embase, Cinahl and
PsycINFO, and the results were summarised and presented to the guideline development group.
12.2 RECOMMENDATIONS FOR RESEARCH

The guideline development group was not able to identify sufficient evidence to answer all of the key questions
asked in this guideline (see Annex 1). The following areas for further research have been identified:
yy S tudies to examine the effect on treatment outcomes of assessing the type, severity and impact of chronic
pain using current validated instruments in primary care.
yy Studies to help identify, at the time of diagnosis, which patients are likely to have poorer outcomes and
whether referring them at an early stage improves outcomes and reduces harms.
yy Investigation of the efficacy of simple approaches to enhancing professional-patient interactions in
consultations in non-specialist settings to improve long-term health outcomes in patients with chronic pain.
yy RCTs on the efficacy of paracetamol in patients with chronic low back pain.
yy Studies of interventions to support reduction or cessation of prescription opioids.
yy Studies of efficacy and harms of opioids beyond three months’ use. Harms potentially include (but are not
restricted to) problematic use, mortality, impact on endocrine and/or immune function, GI effects.
yy Studies of factors affecting individual response to opioid therapy.
yy Studies of harm reduction strategies for patients on continued opioid use for chronic pain.
yy Investigation of strategies for combining drug therapies for optimal efficacy, safety and cost effectiveness.
yy RCTs on the efficacy of pain neurophysiology education.
yy RCTs on the efficacy of acceptance and commitment therapy.
yy Large RCTs on the use of acupuncture compared to standard care or other therapies in reducing pain and
improving quality of life. Researchers should ensure that the acupuncture is carried out by practitioners
who have received professional training. Sham acupuncture is not a suitable comparator.
yy Economic modelling into the cost effectiveness of an acupuncture service.
yy Studies into the use of music in combination with other non-pharmacological therapies in patients with
chronic pain to determine the outcomes of reduction in pain intensity, reduction in use of pharmacological
therapies, and cost effectiveness.
yy RCTs into the use of hypnosis for pain relief.
| 39
yy Studies into the use of herbal medicines, such as harposogide, for pain relief.
yy Investigation into which specific dietary interventions may be beneficial to both specific (eg diabetic
neuropathic pain) and chronic pain conditions in general.
yy Studies into the effect of vitamins A, B6, C, E, omega-3 fatty acids, salts (Ca, Mg, Se, Zn, Fe) and lactic
ferments) in pain relief.
12.3 REVIEW AND UPDATING

This guideline was first published in 2013. Section 5.3 and Annex 4 were updated in 2019. The full guideline
will be considered for update at seven years.
The review history, and any updates to the guideline in the interim period, will be noted in the supporting
material section for this guideline on the SIGN website: www.sign.ac.uk
40 |
13 • Development of the guideline
13 Development of the guideline

13.1 INTRODUCTION
SIGN is a collaborative network of clinicians, other healthcare professionals and patient organisations and
is part of Healthcare Improvement Scotland. SIGN guidelines are developed by multidisciplinary groups of
practising healthcare professionals using a standard methodology based on a systematic review of the evidence.
Further details about SIGN and the guideline development methodology are contained in ‘SIGN 50: A Guideline
Developer’s Handbook’, available at www.sign.ac.uk
13.2 THE GUIDELINE DEVELOPMENT GROUP

Dr Lesley Colvin Consultant in Pain Medicine, Western General Hospital, Edinburgh
(Chair)
Dr Rachel Atherton Clinical Psychologist, Chronic Pain Management Service, NHS Highland
Dr Jonathan Bannister Consultant in Anaesthesia and Pain Medicine, Ninewells Hospital,
Dundee
Ms Janette Barrie Nurse Consultant for Long Term Conditions, NHS Lanarkshire
Dr Heather Cameron Physiotherapy Professional Lead, Western Infirmary, Glasgow
Mr Paul Cameron Clinical Lead Pain Specialist Physiotherapist, NHS Fife Integrated Pain
Management Service
Dr Alan Carson Consultant Neuropsychiatrist, Royal Edinburgh Hospital
Dr Martin Dunbar Consultant Clinical Psychologist, The Pain Management Team, Glasgow
Dr Steve Gilbert Consultant in Anaesthesia and Pain Medicine, Queen Margaret Hospital,
Dunfermline
Dr John Hardman General Practitioner, Dalhousie Medical Practice, Bonnyrigg
Ms Melanie Hutchison Advanced Occupational Therapist, NHS Fife Integrated Pain
Management Service
Mr Malcolm Joss Specialist Occupational Therapist, Occupational Health and Safety
Advisory Services, Rosyth
Professor Arduino Mangoni Professor of Clincial Pharmacology, Flinders University, Australia
Mr Peter McCarron Patient representative, Kelty
Mr Ronald Parsons Patient representative, Leven
Miss Deborah Paton Lead Pharmacist, Pain Management, Lynebank Hospital, Dunfermline
Ms Kathleen Powderly Member of the British Acupuncture Council and Member of the Register
of Chinese Herbal Medicine, Aberdeen
Professor Stuart Ralston Professor of Rheumatology, Western General Hospital, Edinburgh
Dr Mick Serpell Consultant in Pain Medicine, Gartnavel General Hospital, Glasgow
Professor Blair H Smith Professor of Population Science, University of Dundee
Mrs Lynne Smith Evidence and Information Scientist, SIGN
Ms Ailsa Stein Programme Manager, SIGN
Dr John Wilson Consultant in Anaesthesia and Pain Medicine, Royal Infirmary of
Edinburgh
The following group members developed the 2019 update:
Professor Lesley Colvin rofessor of Pain Medicine and Consultant in Anaesthesia and Pain
P
Medicine, NHS Tayside
Professor Blair Smith rofessor of Population Health Sciences and Consultant in Pain Medicine,
P
NHS Tayside
| 41
The membership of the guideline development group was confirmed following consultation with the member
organisations of SIGN. All members of the guideline development group made declarations of interest which
are available in the supporting material section at www.sign.ac.uk.
Guideline development and literature review expertise, support and facilitation were provided by the SIGN
Executive. All members of the SIGN Executive make yearly declarations of interest and further details of these
are available on request.
Mrs Lesley Forsyth Events Co-ordinator
Mrs Karen Graham Patient Involvement Officer
Miss Gemma Hardie Distribution and Office Co-ordinator
Mr Stuart Neville Publications Designer
Miss Gaynor Rattray Guideline Co-ordinator
13.2.1 ACKNOWLEDGEMENTS
SIGN is grateful to the following people who have contributed to the development of the guideline.
Mr Mark Bovey Co-ordinator, Acupuncture Research Resource Centre, British Acupuncture
Council, London
Professor Andrew Moore Deputy Editor, Cochrane Pain, Palliative and Supportive Care Group,
Oxford
13.3 CONSULTATION AND PEER REVIEW
13.3.1 NATIONAL OPEN MEETING

A national open meeting is the main consultative phase of SIGN guideline development, at which the guideline
development group presents its draft recommendations for the first time. The national open meeting for this
guideline was held on 12 December 2012 and was attended by 226 representatives of all the key specialties
relevant to the guideline. The draft guideline was also available on the SIGN website for a limited period at this
stage to allow those unable to attend the meeting to contribute to the development of the guideline.
13.3.2 SPECIALIST REVIEWERS INVITED TO COMMENT ON THIS DRAFT

This guideline was also reviewed in draft form by the following independent expert referees, who were asked to
comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting
the recommendations in the guideline. The guideline group addresses every comment made by an external
reviewer, and must justify any disagreement with the reviewers’ comments. All expert referees made declarations
of interest and further details of these are available on request from the SIGN Executive.
SIGN is very grateful to all of these experts for their contribution to the guideline.
The Association of British Neurologists, London
Dr David Carroll Associate Specialist in Palliative Care and GP Locum, Aberdeen
Mr David Falconer Director, Pain Association Scotland, Perth
Dr Jonathan Hill Research Physiotherapist, Keele University
Mr Simon Land Royal College of Physicians, London
Mrs Kirsty MacFarlane Prinicipal Pharmacist, Scottish Medicines Consortium, Glasgow
Dr Hugh MacPherson Senior Research Fellow in Health Sciences, University of York
Professor Chris Main Professor of Clinical Psychology (Pain Management), Keele University
Ms Cecilia McQuade Patient representative, Glasgow
Dr Barry Miller Consultant in Pain Medicine, Royal Bolton Hospital
Professor Steve Morley Professor of Clinical Psychology, University of Leeds
42 |
13 • Development of the guideline
Mr Paulos Quadros Chief Executive, Intlifepain, Strathaven

Ms Judith Rafferty Lead Advanced Nurse Specialist Pain Management, Ninewells Hospital,
Dundee
Mr Ian Semmons Chairman, Action on Pain, Norfolk
Mrs Heather Wallace Chairman, Pain Concern, Haddington
Dr David Watson General Practitioner, Hamilton Medical Group, Aberdeen
Dr Mike Winter Medical Director, National Services Division, NHSScotland
13.3.3 UPDATE CONSULTATION AND PEER REVIEW

The update was available in draft form on the SIGN website for people to submit comments. It was also reviewed
by the following independent expert reviewers. A report of the consultation and peer review comments and
responses is available in the supporting material section for this guideline on the SIGN website. All expert
referees and other contributors made declarations of interest and further details of these are available on
request from the SIGN Executive.
Ms Emmy Cato-Clark Faculty of Pain Medicine of the Royal College of Anaesthetists
Ms Heather Harrison Senior Prescribing Advisor, Central Prescribing Team, NHS Greater Glasgow
and Clyde
Ms Kathleen Powderly Practitioner of Traditional Chinese and Integrated Healthcare, Aberdeen
Mrs Deborah Steven Lead Pharmacist Pain Management, NHS Fife, Dunfermline
Ms Heather Wallace Chair, Pain Concern, Haddington
13.3.4 SIGN EDITORIAL GROUP

As a final quality control check, the guideline is reviewed by an editorial group comprising the relevant specialty
representatives on SIGN Council to ensure that the specialist reviewers’ comments have been addressed
adequately and that any risk of bias in the guideline development process as a whole has been minimised. The
editorial group for this guideline was as follows. All members of the SIGN Editorial group make yearly declarations
of interest and further details of these are available on request from the SIGN Executive.
Dr Jenny Bennison Royal College of General Practitioners
Professor Keith Brown Chair of SIGN; Co-Editor
Dr Roberta James SIGN Programme Lead; Co-Editor
Dr Rajan Madhok Royal College of Physicians and Surgeons of Glasgow
Ms Fiona McMillan Royal Pharmaceutical Society
Professor Mark Strachan Royal College of Physicians of Edinburgh
Dr Sara Twaddle Director of SIGN; Co-Editor
SIGN editorial group 2019 update:
Dr Jenny Bennison Royal College of General Practitioners
Dr Roberta James SIGN Programme Lead
Dr Rajan Madhok Royal College of Physicians and Surgeons of Glasgow
Mrs Margaret Ryan Royal Pharmaceutical Society
| 43
Abbreviations
ACT acceptance and commitment therapy
BNF British National Formulary
BPI Brief Pain Inventory
BT behavioural therapy
CBT cognitive behavioural therapy
CI confidence interval
CLBP chronic low back pain
COMM Current Opioid Misuse Measure
COX cyclo-oxygenase
CT cognitive therapy
CYPD cytochrome P450 2D6
EMG electromyographic
GI gastrointestinal
GMC General Medical Council
GP general practitioner
GRIPS Getting Relevant Information on Pain Services in Scotland
GTN glyceryl trinitrate
HIV human immunodeficiency virus
HR hazard ratio
HRQOL health-related quality of life
IASP International Association for the Study of Pain
IMMPACT Initiative on Methods, Measurement and Pain Assessment in Clinical Trials
LLLT low-level laser therapy
LOCF last-observation-carried-forward
MA marketing authorisation
MBI mindfulness-based interventions
MBSR mindfulness-based stress reduction
MED morphine equivalent dose
MHRA Medicines and Healthcare products Regulating Agency
MOR mu opioid receptor
MPI Multidimensional Pain Inventory
MT manual therapy
MTA multiple technology appraisal
NICE National Institute for Health and Care Excellence
44 |
Abbreviations
NLR negative likelihood ratio

NNH numbers needed to harm
NNT number needed to treat
NRS numerical rating scale
NSAID non-steroidal anti-inflammatory drug
OA osteoarthritis
OR odds ratio
ORT Opioid Risk Tool
PGIC Patient’s Global Impression of Change
PHN postherpetic neuralgia
PLR positive likelihood ratio
PMP pain management programme
PNE pain neurophysiology education
QoL quality of life
RCT randomised controlled trial
RMDQ Roland Morris Disability Questionnaire
RR relative risk
SAMe S-adenosylmethionine
SD standard deviation
SF-36 short-form with 36 questions
SIGN Scottish Intercollegiate Guidelines Network
SMC Scottish Medicines Consortium
SMD standardised mean difference
SMT spinal manipulation therapy
SNRI serotonin norepinephrine re-uptake inhibitor
SOAPP Screener and Opioid Assessment for Patients with Pain
SPC summary of product characteristics
SRT self-regulatory treatment
SSRI selective serotonin re-uptake inhibitor
TCA tricyclic antidepressant
TENS transcutaneous electrical nerve stimulation
WMD weighted mean difference
| 45
Annex 1
Key questions
This guideline is based on a series of structured key questions that define the target population, the
intervention, diagnostic test, or exposure under investigation, the comparison(s) used and the outcomes used
to measure efficacy, effectiveness, or risk. These questions form the basis of the systematic literature search.
Key question See guideline

section
1. In patients with chronic non-malignant pain presenting in a non-specialist setting, does the use 3.1
of assessment tools lead to improvement in any of the core outcomes of treatment compared
with not using assessment tools?
Outcomes: pain scores (30% reduction and 50% reduction), functional ability, quality of life (mood,
sleep), adverse events
2. In patients with chronic non-malignant pain being managed by any intervention is there any 3.2
evidence that timing of that intervention impacts on pain scores (30% reduction and 50%
reduction), functional ability, quality of life (mood, sleep), adverse events?
3. In patients with chronic non-malignant pain is there any evidence to show that a managed care 3.3
approach can improve pain scores (30% reduction and 50% reduction), functional ability, quality
of life (mood, sleep), adverse events?
Consider: managed care (ie coding chronic pain, call and recall systems, structured protocol-driven
care delivered by nurses or clinicians with a special interest, with active management and regular
reviews of pharmacological treatments, considering when to refer)
4. In patients with chronic non-malignant pain is there any evidence that the nature of interaction 3.4
with healthcare professionals affects pain scores (30% reduction and 50% reduction), functional
ability, quality of life (mood, sleep), adverse events?
Consider: communication, empathy, relationship

5. In patients with chronic non-malignant pain are opioids effective compared with placebo or 5.3
other interventions in pain scores (30% reduction and 50% reduction), functional ability, quality
of life, adverse events/drug reactions, dependency (physiological or psychological)?
Interventions: morphine, diamorphine, oxycodone, hydromorphone, buprenorphine, fentanyl,

methadone, meptazinol, tapentadol, targinact, codeine, dihydrocodeine, tramadol, cocodamol and
codydramol
Exclude: parenteral and neuraxial administration

6. Are there benefits and harms associated with high-dose opioid versus low-dose opioid use in 5.3
patients with chronic non-malignant pain?
Consider: efficacy, pain potentiation, addiction, adverse drug reactions

7. In patients with chronic non-malignant pain what are the most effective simple analgesics 5.2
compared with placebo or other interventions on pain scores (30% reduction and 50%
reduction), functional ability, quality of life, adverse events/drug reactions, dependency
(physiological or psychological)?
Interventions:
a. NSAIDs, COX inhibitors, COX-2s
b. paracetamol
c. nefopam
46 |
Annex 1
8. In patients with chronic non-malignant pain what is the effectiveness of antiepilepsy drugs 5.4, 5.6
reduction), functional ability, quality of life, adverse drug reactions, dependency (physiological
or psychological)?
Interventions:
a. gabapentin
b. pregabalin
c. sodium valproate
d. carbamazepine/oxcarbazepine
e. topiramate
f. lamotrigine
g. lacosamide
h. levetiracetam
9. In patients with chronic non-malignant pain what is the effectiveness of topical analgesics 5.2
Interventions:
a. lidocaine patch
b. capsaicin cream
c. capsaicin patch
d. topical non-steroidals
10. I n patients with chronic non-malignant pain what is the effectiveness of antidepressants 5.5
Interventions:
a. tricyclic antidepressants (amitriptyline, nortriptyliine, clomipramine, imipramine)
b. SSRIs( fluoxetine, citalopram)
c. SNRIs ( duloxetine, mirtazapine, venlafaxine)

11. I n patients with chronic non-malignant pain what is the effectiveness of combination 5.6
pharmacological compared to single pharmacological therapies on pain scores (pain 30%
reduction and 50% reduction), functional ability, quality of life, adverse events/drug reactions,
dependency (physiological or psychological)?
12. I n patients with chronic non-malignant pain what is the effectiveness of physical therapies 7
compared with no physical therapy or other interventions on pain scores (30% reduction and
50% reduction), functional ability, quality of life, adverse events?
Interventions: manual therapy, exercise, massage, traction, electrotherapy
| 47
13. I n patients with chronic non-malignant pain what is the effectiveness of complementary and 8
alternative therapies compared with no treatment or other interventions on pain scores (30%
reduction and 50% reduction), functional ability, quality of life, adverse events?
Interventions:
a. aromatherapy
b. music therapy
c. acupuncture
d. reflexology
e. reiki
f. hypnotherapy
g. homeopathy
h. herbal medicine
14. I n patients with chronic non-malignant pain what is the effectiveness of expert/clinician 6
guided self-help management advice/ programmes/psychological treatments compared with
no treatment or other interventions on pain scores, functional ability, mood, QoL and adverse
events.
Interventions:
a. multidisciplinary pain management programmes based on biopsychosocial principles
b. unidisciplinary education (excluding exercise)
c. first wave psychological treatments: behavioural therapies
(i) respondent behavioural therapies (1) biofeedback (2) relaxation
(ii) operant behavioural therapies
d. second wave psychological treatments: cognitive behavioural therapy
e. third wave psychological treatments: acceptance and commitment

therapy and mindfulness based interventions
Consider: unidisciplinary versus multidisciplinary programmes, mode of delivery, as above;

intensity; who delivers intervention
15. I n patients with non-malignant chronic pain what is the effectiveness of patient and lay self- 4
help advice compared with no treatment or other interventions on pain scores (30% reduction
and 50% reduction), functional ability, quality of life, adverse events?
Interventions:
a. bibliotherapy
b. computer-guided self help
c. structured or guided self help
d. self-help groups versus one-to-one interventions
e. shorter, structured, educational classes
Consider: intensity of programmes, mode of delivery (ie is telephone/video contact as effective as

face-to-face)
48 |
Annex 1
16. I n patients with chronic non-malignant pain is there any evidence for the effectiveness of 9
dietary interventions compared with usual care on pain scores (30% reduction and 50%
reduction), functional ability, quality of life, adverse events?
Interventions:
a. vitamins (B, C, D)
b. omega-3
c. antioxidants
d. glucosamine
e. chondroitin
f. dietary/nutritional supplements or replacements
17. I n patients with chronic non-malignant pain what is the effectiveness of occupational-based No evidence
interventions on pain scores (30% reduction and 50% reduction), functional performance, identified
physical capacity, engagement in personally meaningful occupations, return to work rates,
quality of life, adverse events?
Interventions:
a. analysis of activity/occupational performance
b. purposeful activity as a treatment modality
c. pacing education
d. energy conservation advice
e. establishment of daily routines to improve health and well-being
f. environmental assessment
g. adaptations/equipment provision
h. work/vocational assessments
Consider: Increased independence in activities of daily living, rehabilitative approaches,

participation in occupation, compensatory techniques, occupational performance (self care/work/
leisure), return to employment/vocational rehabilitation
| 49
Annex 2
Pathway for chronic pain assessment, early management and care planning
in non-specialist settings
This pathway is drawn from evidence identified in the guideline, information extrapolated in the research for the guideline and
the clinical experience and consensus of the guideline development group. More detailed pathways on pain assessment and
management are available from the British Pain Society.195
Chronic pain management should focus on non-pharmacological strategies just as much as the use of analgesic drugs. The
prescription of medication is the most convenient element of care but is potentially the most harmful and sometimes the least
effective.
Step 1 Divide assessment and initial management over multiple consultations

Initial Investing time at the initial presentation may improve outcomes for patients and minimise unhelpful use of
assessment resources in future.
Use a patient-centred, culturally sensitive approach
• Explain the treatment options.
• Encourage patients’ involvement in decision making.
Consider red flags
• Consider serious pathology and investigate and refer if necessary.
• Avoid further investigations unless serious pathology is suspected.
• Identify the stage at which no more investigations are planned and explain this clearly to the patient.
Identify the duration of pain
• Make a clear diagnosis of chronic pain where appropriate.
Pain that has been present for more than 12 weeks.
• Record the diagnosis and code it electronically in the patient record.
Identify if there may be an element of neuropathic pain
Typical features: character of pain (burning, shooting), allodynia (pain due to a stimulus that does not
normally provoke pain), hyperalgesia (exaggerated response to a painful stimulus) unpredictable pain, other
abnormal sensations, sensory abnormalities and/or skin changes on clinical examination; symptoms and signs
neuroanatomocally consistent with underlying cause.
Brief validated tools are available to aid diagnosis (eg LANSS, DN4, painDETECT)196 but there is insufficient
evidence to support a recommendation for their routine use.
Assess the severity of pain at different sites
• Use a narrative clinical history to clarify the complexity and intensity of pain.
• Consider using a visual analogue scale or numerical score to help gauge the response to treatment.
Assess functional impact as part of a biopsychosocial assessment
• Consider work, relationships, sleep, mood, disability etc.
The depth of the assessment will depend on the severity of the problem and it may be completed over multiple
consultations.
Identify patients at increased risk of poor outcomes
• Use clinical judgement.
• Consider the use of evidence-based tools (eg Keele STarT Back Tool).
• Be aware of the presence of significant comorbidities.
Mental health problems (including depression, anxiety, personality disorder, post-traumatic stress disorder),
cognitive impairment, substance misuse, pregnancy, polypharmacy, significant renal or hepatic impairment
• Be aware of the presence of yellow flags.
Biomedical Severe pain or increased disability at presentation, previous significant pain episodes, multiple
yellow flags site pain, non-organic signs, iatrogenic factors.
Psychological Belief that pain indicates harm, an expectation that passive rather than active treatments are most
yellow flags helpful, fear avoidance behaviour, catastrophic thinking, poor problem solving ability, passive
coping strategies, atypical health beliefs, psychosomatic perceptions, high levels of distress.
Social Low expectation of return to work, lack of confidence in performing work activities, heavier work,
yellow flags low levels of control over rate of work, poor work relationships, social dysfunction, medico-legal
issues.
50 |
Annex 2
Step 2 Listen, validate, educate, reassure

Interventions • Acknowledge that pain may never entirely resolve.
Encourage a self management approach (see section 4).
Signposting patients to self-management resources should be considered at any stage of their treatment.
The healthcare professional needs to consider which approaches will suit each patient and signpost
them appropriately (see section 10.1). Involve an advocate or carer where possible and relevant, to help
understanding and motivate for change.
Advise the patient to stay active
• Consider referral for:
{{exercise therapy where available (see section 7.2)
{{manual therapy (eg physiotherapy, TENS; see sections 7.1, 7.4), or
{{acupuncture where available (see section 8.1).
Support the patient to stay at work

• Consider occupational health referral and benefits advice.
Treat the underlying cause of pain where possible
• Encourage appropriate use of over-the-counter analgesics (see section 5.2).
• Be aware that treatment of moderate or severe depression (where present) may reduce pain (see section
5.5.4).
Step 3 Conduct a more comprehensive biopsychosocial assessment, where possible, for patients at increased
Additional risk of poor outcomes
interventions
Biomedical Thorough pain history assessing each discrete pain experienced by the patient (site, character,
assessment intensity, onset, precipitants, duration, intensity, exacerbating and relieving factors, night pain,
perceived cause), systemic symptoms, past medical history, physical examination (including
behavioural response to examination); previous investigations (and patient’s understanding);
previous and current treatment (including response, specialist treatments, side effects,
misconceptions, fixed beliefs, messages from other health professionals).
Psychological Consider low mood, anxiety or depression; psychiatric history, alcohol and illicit drug use, misuse,
assessment dependence or addiction, history of physical or sexual abuse; identify yellow flags (see above),
loss of confidence, poor motivation, reluctance to modify lifestyle, unrealistic expectations of self
and others.
Social Ability to self care, occupational performance, influence of family on pain behaviour,
assessment dissatisfaction at work, secondary gain (family overprotection, benefits, medico-legal
compensation).
Agree a pain management plan
eg verbal agreement of a single goal, and how to achieve it, or a self-directed written plan.
• C
onsider early referral to secondary care where pain is severe, not responding adequately to
management, or for specific specialist assessment and/or treatments.
| 51
Step 4 Before prescribing analgesic drugs

Analgesic • Offer non-pharmacological strategies in addition to, or as alternative to, analgesic drugs.
drugs
• Agree the goals of therapy eg reduction in pain, improved mood, improved function.
• Agree the length of the initial trial.
• Discuss the potential side effects of all drugs prescribed.
• Discuss the significant risks of specific drugs, especially NSAIDs and opioids.
• Discuss the short-term benefits and potential loss of efficacy over time before prescribing opioids.
• Avoid co-prescription of sedative and hypnotic medication where possible and be aware of concomitant
alcohol use.
• Be aware of concomitant use of over-the-counter treatments, and advise accordingly.
For patients who continue to have poorly controlled pain
• Schedule review appointments rather than allowing them to be dictated by pain levels.
• Plan management of exacerbations.
• Consider trialling two or three other drugs from the same class if the first is ineffective.
• Down-titrate or withdraw ineffective treatments.
• Consider rational multimodal analgesia: avoid coprescription of drugs from within the same class,
consider the safety and logic of the prescribing regimen when combining drug treatments.
After commencing drug treatment
• I ncrease to the recommended starting dose then titrate against response where appropriate, up to the
recommended maximum dose, unless limited by side effects.
• Review the efficacy of all drugs after an initial trial at the optimum dose, usually after two weeks (up to
four weeks for antidepressants), using the narrative clinical history, a visual analogue scale or numerical
scores.
Most individuals respond in one of two ways: either a good response (at least 30% improvement) or no
response.
Choice of drug
• Use the WHO ladder pragmatically and do not continue prescribing drugs that are ineffective.
• If neuropathic pain appears to be present follow the pathway for patients with neuropathic pain
(see Annex 3).
Choice of individual drug or combination will be influenced by:
-- severity of pain
-- presence of neuropathic pain
-- comorbidity and coprescribing
-- risk of drug misuse
-- previous drug efficacy
-- previous adverse effects
-- interactions with other prescribed medication
-- clinician experience.
• Use as first line:
{{paracetamol (see section 5.2)
{{NSAIDs (see section 5.2)
• Also consider:
{{weak opioids (see section 5.3)
{{topical NSAIDs (see section 5.2)
{{topical rubefacients (see section 5.2.7).
• If pain still not controlled:
{{reconsider non-pharmacological strategies (see sections 6,7 and 8)
{{refer to the pathway for using strong opioids (see Annex 4).
52 |
Annex 2
Step 5 Consider onward referral

Referral • To psychologically based therapies (includes CBT, behavioural therapies, mindfulness meditation,
acceptance and commitment therapy); (see section 6) when the patient:
{{has moderate to high levels of distress
{{has difficulty adjusting to a life with pain
{{is struggling to change their behaviour to maintain normal activities.
For patients with pre-existing emotional problems, discuss any proposed referral with their current care
provider or with the team who will be providing the new therapy. The discussion should review the outcomes of
previous therapeutic interventions and consider whether the patient is likely to benefit.
Selection of a particular therapeutic approach is likely to be determined by local availability, but consider the
patients’ preferences where a choice is available.
• To specialist pain service if:
{{there is treatment failure after trial of four drugs for neuropathic pain
{{the opioid dose is greater than 180 mg morphine per day or equivalent
{{there is an inadequate response to non-specialist management.
• To a multidisciplinary pain management programme (see section 6.1) when the patient has:
{{poor functional capacity
{{moderate to high levels of distress
{{social and occupational problems related to pain
{{failed to benefit from other, less comprehensive therapies
{{a preference for a self management rather than a medical approach.
Delaying referral until other treatment avenues are exhausted can be dispiriting and unhelpful. Ensure
that patients are aware that PMP will be a group-based treatment focused on improving quality of life and
participation in normal activities. It is also important that the patient understands the likely composition of the
PMP team.
Step 6 Initial review

Review • Once stability is achieved an initial review should take place no more than six months later.
Subsequent reviews
• Subsequent reviews should be at least annual.
• At each review reassess medication concordance and efficacy, adverse effects, alcohol and illicit drug use,
mood, function and review the management plan if appropriate.
• Consider using a recall system to facilitate annual reviews.
Step 7 Reassessment
Exacerbations • Consider reassessment for new or worsening pathology and the possible need for further investigation.
• Plan for the use of non-pharmacological strategies.
• Avoid the use of short-acting strong opioids.
Routine use during exacerbations may increase tolerance and may lead to dose escalation.
• Down-titrate analgesics between exacerbations.
Reassurance
• Reassure the patient that exacerbations are common, are not necessarily indicative of a worsening of their
underlying condition and are likely to settle quickly.
Reviewing previous episodes may be helpful.
• Reassure the patient that it is safe to maintain normal activities of daily living at a moderate level.
• Discourage patients from resting excessively during an exacerbation.
| 53
Annex 3
Pathway for patients with neuropathic pain
Step 1 •• Make a clinical diagnosis based on history, signs and symptoms

Diagnosis •• Screening questionnaires can be used to aid the process (see Annex 2 for pathway on assessment
and early management of chronic pain)
Diagnosis of neuropathic pain is a clinical diagnosis but may be aided by one of the various available
questionnaires.
Common causes are postherpetic neuralgia and diabetic peripheral neuropathy but there are
many other causes including postsurgical nerve dysfunction, cancer, trigeminal neuralgia, HIV,
postamputation pain, multiple sclerosis etc.
Once a diagnosis is made, then it is usual to start an initial systemic drug. Review should be frequent to
optimise drug dosage and to improve tolerability. Drugs that are having little useful effect after a dose
titration should be stopped and an alternative tried.
Step 2 •• Amitriptyline
Initial agents •• Gabapentin
The drug to use first depends mainly on clinical preference. There is no strong evidence to choose
one over the other. Prescriber preference, experience and patient factors should all be considered.
If the first agent chosen is not helpful, then an alternative may be used either as a sole agent or in
combination.
In clinical practice the usual step one systemic drug is a tricyclic antidepressant such as amitriptyline
or a gabapentinoid.
Amitriptyline (see section 5.5)
The suggested efficacious dose range for amitriptyline is 25-125 mg. In many patients it may be
beneficial to start with only 10 mg and titrate upwards. The dose should be increased by 10 mg per
week until either efficacy is achieved or the patient cannot tolerate the drug. Dosages higher than 125
mg are sometimes used in clinical practice but evidence for these doses is lacking.
Amitriptyline, in common with the other TCAs, has a number of side effects. One of the common
reasons for discontinuation is excessive drowsiness.
Gabapentinoids (see section 5.4)
Gabapentin is normally the gabapentinoid of choice. It is usually started at 300 mg at night and
titrated upwards (increasing by 300 mg per week is suggested). Evidence suggests that a minimum
of 1,200 mg is needed. Doses may need to be increased as high as 3,600 mg. This is consistent with
published clinical trials.
Pregabalin (see section 5.4.2)
Pregabalin is an alternative in patients who have have found no benefit from or not tolerated
amitriptyline or gabapentin. It is usually started at a dose of 75 mg twice daily. In some patients
smaller starting doses may be used but doses of 150 mg daily are generally ineffective. The drug may
be titrated up until a maximal dose of 300 mg twice daily is reached. The dose should be titrated
according to effect and with the side effects in mind as a flexible dosing has been shown to be
better. Common side effects are somnolence and dizziness. (The SMC recommends that pregabalin is
reserved for patients who have not tolerated or who have failed on a conventional first- or second-line
agent, for example a TCA or gabapentin; see section 11.4).
54 |
Annex 3
Step 3 •• Alternative tricyclic antidepressants

Alternative agents •• SNRI antidepressants
Alternative systemic drugs (see section 5.6)
If initial agents do not help it is appropriate to change to an alternative agent, either as a sole agent
or in combination with one or more drugs known to be effective in neuropathic pain, such as a
gabapentinoid (or opioid in appropriate cases). Generally two types of antidepressant are not given
together unless one is in low dose (eg amitriptyline 25 mg) or on specialist advice.
Alternative TCAs (see section 5.5.1)
If amitriptyline does not produce effective results, then an alternative TCA such as impramine or
nortriptyline may be used. These may be less sedating and better tolerated but are not any more
efficacious. Dosages are normally in the range of 25-75 mg daily.
SNRI antidepressants (see section 5.5.2)
Duloxetine is the SNRI most commonly used for neuropathic pain. The recommended dose of
duloxetine is 60 mg per day in a single dose (doses up to 120 mg have been used).
Alternative antiepilepsy drugs (see sections 5.4.3 and 5.4.4)
Although many antiepilepsy drugs have been used in the treatment of neuropathic pain, apart from
carbamazepine, there is little evidence to support their use. Carbamazepine should be used as a
first-line agent in patients with trigeminal neuralgia. It may also be used in patients with general
neuropathic pain. In both cases the initial dose should be 100-200 mg daily increasing slowly in
increments of 100-200 mg biweekly. Doses up to 1,600 mg daily have been used.
Step 4 •• Topical lidocaine plasters

Topical agents
In patients with localised neuropathic pain it may be appropriate to use a topically acting agent (see
sections 5.2.4 to 5.2.7).
Topical lidocaine plasters (see section 5.2.6)
Topical lidocaine plasters are the topical agent of choice (in the non-specialist setting) in patients who
prefer a topical treatment. Up to three plasters can be used at a time. These are worn 12 hours on and
12 hours off. There are few side effects apart from some skin reddening and irritation. If there is no
improvement after four weeks, then they should be discontinued.
Low-dose topical capsaicin
There is no good evidence for the use of low-dose topical capsaicin (see section 5.2.5; see Step 6
regarding high-dose capsaicin patch).
Step 5 •• Opioids
Opioids Opioids (see section 5.3)
•• Use only in carefully selected and screened patients
•• Use long-acting preparations only. Avoid breakthrough dosing
•• Prescribe no higher than 180 mg morphine (or equivalent) without specialist advice
•• Discontinue if not effective
•• Follow the pathway for using strong opioids (see Annex 4).
Step 6 •• Tertiary drugs (capsaicin 8% patch, ketamine)

Specialist referral •• Specialised interventions
•• Multidisciplinary assessment with appropriate psychological therapies
Patients with refractory pain (pain unresponsive after four or more conventional drug therapies) or
patients failing on opioids should be referred for specialist advice. Tertiary options include the use of
capsaicin 8% patch (see section 5.2.5), interventional procedures, drugs such as ketamine and a robust
multidisciplinary approach which includes appropriate psychological therapies.
| 55
Annex 4
Pathway for using strong opioids in patients with chronic pain
Strong opioids should only be considered after a full assessment and as part of a wider management plan, rather than as sole
agents. Prescribers should have knowledge of opioid pharmacology and be competent and experienced in the use of strong
opioids.
Pathway: pages 57–59
Annex 4 Management of chronic pain of chronic pain

Management Annex 4
1. Assess suitability for strong opioid use 2. Starting a strong opioid 3. Monitoring opioid trial
Assess pain Aim to establish the patient on a long-acting opioid with no immediate At all times before and during opioid treatment signs of iatrogenic
release opioid if the chronic pain is stable. For mild ‘breakthrough pain’ substance misuse should be sought.
consider non-opioids (eg paracetamol, NSAIDs); a weak opioid. If problems arise consider early specialist advice.
Assess pain relief

Consider:
Is the pain likely
to respond to an opioid • Choice of opioid i F
eg nociceptive with Avoid opioids
• Route of administration. Oral and transdermal are the main
some benefit from No routes for chronic non-malignant pain. Is pain relief
a weak opiod?
Pain is unlikely to adequate?
• Dose. There is considerable variability in the dose needed to
respond to strong
effectively treat pain. Careful titration to the lowest effective dose,
opioid eg neuropathic;
Consider specialist balanced against side effects, requires regular review. If >90 mg
no analgesia from
advice morphine equivalent dose/day seek specialist advice.
weak opioids
Yes
Inadequate No response Adequate

Consider opioid trial
on a stable dose
Potential regimens (use one at a time): of opioid without
unacceptable
• Start with low dose of long-acting preparation. If the patient is already
side effects
on an opioid such as cocodamol or dihydrocodeine then they are not
Assess the patient opioid naive, particularly if on a high dose of one or more of these
i A
agents.
Increase analgesic Reduce and STOP analgesic
• Relevant psychosocial factors dose and tritate to
• Risk factors for iatrogenic dependency • While establishing dose, use an immediate-release preparation for response
• Other comorbidities short-term use only, to determine approximate dose range, then convert Continue current
to equivalent long-acting preparation as soon as possible. This may be analgesic therapy
• Other analgesics.
more appropriate if the patient has multiple comorbidities.
Ask patient
about adverse Review at least annually, more frequently
Discussion with the patient: analgesic effects if problems arise, ideally with one
• Provide information leaflets i B Treat if possible prescriber. The review should include dose,
• Establish goals of treatment effectiveness and adverse effects.
Be aware that opioids should NOT be used i C i G
If using ≥90 mg morphine equivalent dose/
as anxiolytics day seek specialist advice.
• Discuss the side effects/potential problems. i D
Is patient
No Have a clear and comprehensive
experiencing drug-
Define how the trial will work flare up plan.
related adverse
• Set a timescale including: effects?
expected duration of trial frequency of review.
• Set a dose including:

the upper dose limit and aim for lowest i E Yes
effective dose.
• Agree stopping rules with the patient before starting:

Consider opioid conversion
- if the treatment goals are not met
• Short-acting opioids may need to be used during the
- if there is no clear evidence of dose response conversion both to reduce physical withdrawal and while
- if rapid tolerance develops necessitating high-dose optimum dose is being established.
opioids. Under these circumstances proceed
• If the patient is on a large dose of opioids, consider phased
to reduction and cessation, or consider specialist
conversion, eg gradual reduction of the current opioid dose
referral/advice.
to 50% and introduce the new opioid dose at less than the
morphine equivalent dose because of incomplete cross-
reactivity.
• Continue with reduction of the old opioid and increase in

new opioid as indicated by response.
| 57 58 | | 59
Information and boxes 1 and 2: pages 60–61
Management of chronic pain of chronic pain

Management Annex 4
i Box 2: Suggested dose conversion ratios

A Relevant psychosocial factors: E International Association for the Study of Pain (IASP)
• children in house statement on prescribing opioids (link)
(converting from) (converting to) Divide 24 hour dose* of current opioid (column 1) by
• other family members with a history of substance misuse
F See boxes 1 and 2 for choice of opioid and suggested dose Current opioid New opioid and/or new route relevant figure below to calculate initial 24 hour dose
problems.
conversion ratios of administration of new opioid and/or new route (column 2)
Risk factors for iatrogenic dependency:
• history of heroin abuse G Preventing and managing adverse effects Divide by 3
Example
• history of alcohol abuse Gastrointestinal (120 mg / 3 = 40 mg subcutaneous diamorphine in 24
120 mg oral morphine in 24 hours subcutaneous diamorphine
• history of stimulant use • Nausea/vomiting: tolerance usually develops. Consider hours)
• mental health problems. use of an antiemetic at initiation of therapy. Avoid ORAL TO ORAL ROUTE CONVERSIONS
cyclizine if possible due to the potential of abuse.
Other comorbidities: oral codeine oral morphine Divide by 10
• Constipation: tolerance often does not develop to this.
• cognitive impairment – cognitive side effects are more Use stool softeners/stimulant laxatives or a combination.
likely; concordance and safety may be an issue Consider opioid preparations less likely to cause GI oral tramadol oral morphine Divide by 5
• renal impairment – accumulation of active metabolites with effects.
some opioids oral morphine oral oxycodone Divide by 2
Central nervous system
• gastrointestinal pathology – adverse effect on bowel function. oral morphine oral hydromorphone Divide by 7.5
If these do not resolve, then either dose reduction or
Other analgesics: conversion will be needed.
ORAL TO TRANSDERMAL ROUTE CONVERSIONS
• use simple analgesics, topical therapies and antineuropathic • Impaired memory, concentration
agents (if appropriate) for opioid sparing effect. • Hallucinations, milder visual disturbance oral morphine transdermal fentanyl Refer to manufacturer’s information**
• Sedation, confusion, cognitive impairment
B SIGN patient booklet oral morphine transdermal buprenorphine Seek specialist palliative care advice
• Myoclonic jerks.
C Primary goals: Other ORAL TO SUBCUTANEOUS ROUTE CONVERSIONS
• pain relief (define the degree that would be acceptable to • Sweating
the patient) oral morphine subcutaneous morphine Divide by 2
• Reduced libido, fertility. Consider stopping,
Secondary goals: testosterone replacement, possible opioid conversion; oral morphine subcutaneous diamorphine Divide by 3
• improved function, sleep, mood. may need endocrine review.
• Respiratory depression. Stop opioid until resolves; oral oxycodone subcutaneous morphine No change
D The patient needs to be aware of the potential side effects consider factors contributing to event.
and they need to be acceptable to the patient, eg: oral oxycodone subcutaneous oxycodone Divide by 2
• Tolerance. Rotate opioid or reduce and stop.
• GI dysfunction (nausea, vomiting, constipation)
• Opioid induced hyperalgesia. Rotate opioid or reduce oral oxycodone subcutaneous diamorphine Divide by 1.5
• central nervous system (memory and cognitive impairment, and stop; seek specialist advice.
nightmares, hallucinations, visual disturbance) subcutaneous
oral hydromorphone Seek specialist palliative care advice
• endocrine (fertility, sexual function) hydromorphone
• immune function OTHER ROUTE CONVERSIONS RARELY USED IN PALLIATIVE MEDICINE
• misuse potential
subcutaneous or intramuscular
• tolerance intravenous morphine No change
morphine
• opioidinduced hyperalgesia.
intravenous morphine oral morphine Multiply by 2
Box 1: Choice of opioid oral morphine intramuscular morphine Divide by 2
OPIOID ROUTE COMMENTS Conversion ratios between strong opioids: Strong evidence for converting between opioids is lacking, with the majority of
Morphine Oral Most commonly used; very variable bioavailability (15 - 65%), no evidence that it is studies being single dose, small sample size pharmacokinetic studies, usually in healthy volunteers (see section 12.2). A number
better than other opioid; active metabolites can accumulate in renal impairment, of dose conversion charts are available and can be useful, but there is significant inter-individual variability and they should be
some may cause hyperalgesia. used with caution, particularly in the elderly; if there are significant other co-morbidities (eg hepatic or renal impairment); or
with polypharmacy.
Tramadol Oral weak MOR agonist (~1/6000th that of morphine) with additional effects on
noradrenergic and serotonergic systems. Metabolism is via the CYPD, with one of the
active metabolites: O-desmethyltramadol having considerably more potency at the * The same units must be used for both opioids or routes, eg mg morphine to mg oxycodone
MOR. ** The conversion ratios of oral morphine:transdermal fentanyl specified by the manufacturer(s) vary from
around100:1 to 150:1
Oxycodone Oral More reliable bioavailability than morphine (60 - 87%); metabolism involves CYPD.
Fentanyl Transdermal Useful if problems with oral administration.
Buprenorphine Transdermal Useful if problems with oral administration; minimal active metabolite accumulation
in renal impairment.
Hydromorphone Oral Potent strong opioid, metabolised in the liver. Wide inter-individual patient
variability.
Tapentadol Oral New opioid with additional activity on the noradrenergic systems; may have a role in
neuropathic pain; some evidence of improved side effect profile and drop-out rates
from RCTs compared to other strong opioids.
Oxycodone/ Oral Combined preparation where naloxone binds preferentially to MORs in the GI
Naloxone tract, with potential reduction in opioid-related adverse GI effects. Maximum
recommended dose 80 mg oxycodone/40 mg naloxone.
Methadone Oral Very unpredictable pharmacokinetics with considerable inter-individual variation.
NOT recommended for use without specialist advice.
60 | | 61
56 |
Annex 4
1. Assess suitability for strong opioid use
Assess pain
Is the pain likely

to respond to an opioid
eg nociceptive with Avoid opioids
some benefit from No
a weak opiod?
Pain is unlikely to
respond to strong
opioid eg neuropathic;
no analgesia from Consider specialist
weak opioids advice
Yes
Consider opioid trial
Assess the patient

i A
• Relevant psychosocial factors
• Risk factors for iatrogenic dependency
• Other comorbidities
• Other analgesics.
Discussion with the patient:

• Provide information leaflets i B
• Establish goals of treatment
Be aware that opioids should NOT be used i C
as anxiolytics
• Discuss the side effects/potential problems. i D
Define how the trial will work

•
Set a timescale including:
expected duration of trial frequency of review.
•
Set a dose including:
the upper dose limit and aim for lowest i E
effective dose.
•
Agree stopping rules with the patient before starting:
- if the treatment goals are not met
- if there is no clear evidence of dose response
- if rapid tolerance develops necessitating high-dose
opioids. Under these circumstances proceed
to reduction and cessation, or consider specialist
referral/advice.
| 57
2. Starting a strong opioid
Aim to establish the patient on a long-acting opioid with no immediate

release opioid if the chronic pain is stable. For mild ‘breakthrough pain’
consider non-opioids (eg paracetamol, NSAIDs); a weak opioid.
Consider:
• Choice of opioid i F
• Route of administration. Oral and transdermal are the main
routes for chronic non-malignant pain.
• Dose. There is considerable variability in the dose needed to

effectively treat pain. Careful titration to the lowest effective dose,
balanced against side effects, requires regular review. If >90 mg
morphine equivalent dose/day seek specialist advice.
Potential regimens (use one at a time):

• Start with low dose of long-acting preparation. If the patient is already
on an opioid such as cocodamol or dihydrocodeine then they are not
opioid naive, particularly if on a high dose of one or more of these
agents.
• While establishing dose, use an immediate-release preparation for

short-term use only, to determine approximate dose range, then convert
to equivalent long-acting preparation as soon as possible. This may be
more appropriate if the patient has multiple comorbidities.
58 |
Annex 4
3. Monitoring opioid trial
At all times before and during opioid treatment signs of iatrogenic

substance misuse should be sought.
If problems arise consider early specialist advice.
Assess pain relief
Is pain relief
adequate?
Inadequate No response Adequate

on a stable dose
of opioid without
unacceptable
side effects
Increase analgesic Reduce and STOP analgesic

dose and tritate to
response
Continue current
analgesic therapy
Ask patient
about adverse Review at least annually, more frequently
analgesic effects if problems arise, ideally with one
Treat if possible prescriber. The review should include dose,
effectiveness and adverse effects.
i G
If using ≥90 mg morphine equivalent dose/
day seek specialist advice.
Is patient
No Have a clear and comprehensive
experiencing drug-
flare up plan.
related adverse
effects?
Yes
Consider opioid conversion

•S
hort-acting opioids may need to be used during the
conversion both to reduce physical withdrawal and while
optimum dose is being established.
• If the patient is on a large dose of opioids, consider phased

conversion, eg gradual reduction of the current opioid dose
to 50% and introduce the new opioid dose at less than the
morphine equivalent dose because of incomplete cross-
reactivity.
•C
ontinue with reduction of the old opioid and increase in
new opioid as indicated by response.
| 59
i
A Relevant psychosocial factors: E International Association for the Study of Pain (IASP)
• children in house statement on prescribing opioids. http://www.iasp-pain.
org/Advocacy/Content.aspx?ItemNumber=7194
• other family members with a history of substance misuse
problems.
F See boxes 1 and 2 for choice of opioid and suggested dose
Risk factors for iatrogenic dependency: conversion ratios
• history of heroin abuse
G Preventing and managing adverse effects
• history of alcohol abuse
• history of stimulant use Gastrointestinal
• mental health problems. •N
ausea/vomiting: tolerance usually develops. Consider
use of an antiemetic at initiation of therapy. Avoid
Other comorbidities: cyclizine if possible due to the potential of abuse.
• cognitive impairment – cognitive side effects are more •C
onstipation: tolerance often does not develop to this.
likely; concordance and safety may be an issue Use stool softeners/stimulant laxatives or a combination.
• renal impairment – accumulation of active metabolites with Consider opioid preparations less likely to cause GI
some opioids effects.
• gastrointestinal pathology – adverse effect on bowel function. Central nervous system
Other analgesics: If these do not resolve, then either dose reduction or
• use simple analgesics, topical therapies and antineuropathic conversion will be needed.
agents (if appropriate) for opioid sparing effect. • Impaired memory, concentration
•H
allucinations, milder visual disturbance
B SIGN patient booklet
•S
edation, confusion, cognitive impairment
C Primary goals: •M
yoclonic jerks.
• pain relief (define the degree that would be acceptable to Other
the patient) • Sweating
Secondary goals: •R
educed libido, fertility. Consider stopping,
• improved function, sleep, mood. testosterone replacement, possible opioid conversion;
may need endocrine review.
D The patient needs to be aware of the potential side effects •R
espiratory depression. Stop opioid until resolves;
and they need to be acceptable to the patient, eg: consider factors contributing to event.
• GI dysfunction (nausea, vomiting, constipation) •T
olerance. Rotate opioid or reduce and stop.
• central nervous system (memory and cognitive impairment, •O
pioid induced hyperalgesia. Rotate opioid or reduce
nightmares, hallucinations, visual disturbance) and stop; seek specialist advice.
• endocrine (fertility, sexual function)
• immune function
• misuse potential
• tolerance
• opioid-induced hyperalgesia.
Box 1: Choice of opioid

OPIOID ROUTE COMMENTS
Morphine Oral Most commonly used; very variable bioavailability (15–65%), no evidence that it is
better than other opioid; active metabolites can accumulate in renal impairment,
some may cause hyperalgesia.
Tramadol Oral Weak MOR agonist (~1/6000th that of morphine) with additional effects on
noradrenergic and serotonergic systems. Metabolism is via CYPD, with one of the
active metabolites: O-desmethyltramadol having considerably more potency at
the MOR.
Oxycodone Oral More reliable bioavailability than morphine (60–87%); metabolism involves CYPD.
Fentanyl Transdermal Useful if problems with oral administration.
Buprenorphine Transdermal Useful if problems with oral administration; minimal active metabolite accumulation
in renal impairment.
Hydromorphone Oral Potent strong opioid, metabolised in the liver. Wide interindividual patient variability.
Tapentadol Oral New opioid with additional activity on the noradrenergic systems; may have a role in
neuropathic pain; some evidence of improved side effect profile and drop-out rates
from RCTs compared to other strong opioids.
Oxycodone/ Oral Combined preparation where naloxone binds preferentially to MORs in the GI
Naloxone tract, with potential reduction in opioid-related adverse GI effects. Maximum
recommended dose 80 mg oxycodone/40 mg naloxone.
Methadone Oral Very unpredictable pharmacokinetics with considerable interindividual variation.
NOT recommended for use without specialist advice.
60 |
Annex 4
Box 2: Suggested dose conversion ratios
(converting from) (converting to) Divide 24 hour dose* of current opioid (column 1) by
Current opioid New opioid and/or new route relevant figure below to calculate initial 24 hour dose
of administration of new opioid and/or new route (column 2)
Divide by 3
Example
(120 mg / 3 = 40 mg subcutaneous diamorphine in 24
120 mg oral morphine in 24 hours subcutaneous diamorphine
hours)
ORAL TO ORAL ROUTE CONVERSIONS
oral codeine oral morphine Divide by 10
oral tramadol oral morphine Divide by 5
oral morphine oral oxycodone Divide by 2
oral morphine oral hydromorphone Divide by 7.5
ORAL TO TRANSDERMAL ROUTE CONVERSIONS
oral morphine transdermal fentanyl Refer to manufacturer’s information**
oral morphine transdermal buprenorphine Seek specialist palliative care advice
ORAL TO SUBCUTANEOUS ROUTE CONVERSIONS
oral morphine subcutaneous morphine Divide by 2
oral morphine subcutaneous diamorphine Divide by 3
oral oxycodone subcutaneous morphine No change
oral oxycodone subcutaneous oxycodone Divide by 2
oral oxycodone subcutaneous diamorphine Divide by 1.5
subcutaneous
oral hydromorphone Seek specialist palliative care advice
hydromorphone
OTHER ROUTE CONVERSIONS RARELY USED IN PALLIATIVE MEDICINE
subcutaneous or intramuscular
intravenous morphine No change
morphine
intravenous morphine oral morphine Multiply by 2
oral morphine intramuscular morphine Divide by 2
Conversion ratios between strong opioids: Strong evidence for converting between opioids is lacking, with the majority
of studies being single dose, small sample size pharmacokinetic studies, usually in healthy volunteers. A number of dose
conversion charts are available and can be useful, but there is significant interindividual variability and they should be used
with caution, particularly in the elderly; if there are significant other comorbidities (eg hepatic or renal impairment); or with
polypharmacy.
An alternative dose conversion table is available from The Faculty of Pain Medicine, www.rcoa.ac.uk/faculty-of-pain-medicine/
opioids-aware/structured-approach-to-prescribing/dose-equivalents-and-changing-opioids
* The same units must be used for both opioids or routes, eg mg morphine to mg oxycodone
** The conversion ratios of oral morphine:transdermal fentanyl specified by the manufacturer(s) vary from
around 100:1 to 150:1
| 61
Annex 5
Scottish service model for chronic pain
Chronic Pain Scotland

Service Model
Most people get back to normal after pain that might come on after an injury or
operation or for no apparent reason. Sometimes the pain carries on for longer than
12 weeks despite medication or treatment – this is called chronic or persistent pain.
1 Level 1 - Advice and information

about pain and what to do about
it. Anyone can access these
services from home or
community settings
2 Level 2 - When help from a GP or

therapist is needed
Level 3 - For those needing more

specialist help from a chronic
3 pain management service
Level 4 - Highly specialised help

4
Information and guidance supporting all levels

Visit www.chronicpainscotland.org
62 |
References
References 16. Rowbotham MC. Mechanisms of neuropathic pain and their

implications for the design of clinical trials. Neurology 2005;65(12
Suppl 4):S66-73.
1. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey 17. Dworkin RH, Turk DC, Peirce-Sandner S, Baron R, Bellamy N,
of chronic pain in Europe: prevalence, impact on daily life, and Burke LB, et al. Research design considerations for confirmatory
treatment. Eur J Pain 2006;10(4):287-333. chronic pain clinical trials: IMMPACT recommendations. Pain
2010;149(2):177-93.
2. Elliott A, Smith BH, Penny KI, Smith WC, Chambers WA. The
epidemiology of chronic pain in the community. Lancet 18. McQuay H, Moore A. Utility of clinical trial results for clinical
1999;354(9186):1248-52. practice. Eur J Pain 2007 11(2):123-4.
3. Sjogren P, Ekholm O, Peuckmann V, Gronbaek M. Epidemiology of 19. Moore RA, Derry S, McQuay HJ, Straube S, Aldington D, Wiffen P, et
chronic pain in Denmark: an update. Eur J Pain 2009;13(3):287-92. al. Clinical effectiveness: an approach to clinical trial design more
relevant to clinical practice, acknowledging the importance of
4. Toblin RL, Mack KA, Perveen G, Paulozzi LJ. A population-based individual differences. Pain 2010;149(2):173-6.
survey of chronic pain and its treatment with prescription drugs.
Pain 2011;152(6):1249-55. 20. Dworkin RH, Turk DC, Katz NP, Rowbotham MC, Peirce-Sandner
S, Cerny I, et al. Evidence-based clinical trial design for chronic
5. Maniadakis N, Gray A. The economic burden of back pain in the pain pharmacotherapy: a blueprint for ACTION. Pain 2011;152(3
UK. Pain 2000;84(1):95-103. Suppl):S107-15.
6. Reginster JY. The prevalence and burden of arthritis. Rheumatology 21. McQuay HJ, Derry S, Moore RA, Poulain P, Legout V. Enriched
2002;41(Supp 1):3-6. enrolment with randomised withdrawal (EERW): Time for a new
look at clinical trial design in chronic pain. Pain 2008;135(3):217-20.
7. NHS Quality Improvement Scotland. Getting to GRIPS with
chronic pain in Scotland: getting relevant information on
22. Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP,
pain services. Edinburgh: NHS Quality Improvement Scotland;
Katz NP, et al. Core outcome measures for chronic pain clinical
2008. [cited 18 Oct 2013]. Available from url: http://www.
trials: IMMPACT recommendations. Pain 2005;113(1-2):9-19.
healthcareimprovementscotland.org/our_work/long_term_
conditions/programme_resources/getting_to_grips_with_ 23. Turk DC, Dworkin RH. What should be the core outcomes in chronic
chronic.aspx pain clinical trials? Arthritis Res Ther 2004;6(4):151-4.
8. Scottish Government. Management of chronic pain in children 24. Moore RA, Straube S, Eccleston C, Derry S, Aldington D, Wiffen
and young people: a national clinical guideline. Edinburgh: The P, et al. Estimate at your peril: imputation methods for patient
Scottish Government; 2018. [cited 19 Aug 2019] Available from url withdrawal can bias efficacy outcomes in chronic pain trials using
https://www.sign.ac.uk/assets/chronic_pain_in_children.pdf.pdf responder analyses. Pain 2012;153(2):265-8.
9. Scottish Intercollegiate Guidelines Network (SIGN). Management 25. Guidance on prescribing. In: The British National Formulary No.
of early rheumatoid arthritis. Edinburgh: SIGN; 2011. (SIGN 61. London: British Medical Association and Royal Pharmaceutical
publication no.123). [cited 18 Oct 2013]. Available from url: http:// Society of Great Britain; 2012.
www.sign.ac.uk/guidelines/fulltext/123/index.html
26. electronic Medicines Compendium (eMC). [cited 22 October 2013].
10. Scottish Intercollegiate Guidelines Network (SIGN). Management Available from url: www.medicines.org.uk
of sore throat and indications for tonsillectomy. Edinburgh: SIGN;
2010. (SIGN publication no.117). [cited 18 Oct 2013]. Available from 27. Medicines and Healthcare products Regulatory Agency. Off-label
url: http://www.sign.ac.uk/guidelines/fulltext/117/index.html use or unlicensed medicines: prescribers’ responsibilities. Drug
Safety Update 2009;2(9):6-7.
11. Scottish Intercollegiate Guidelines Network (SIGN). Pharmacological
management of migraine. Edinburgh: SIGN 2018. (SIGN publication 28. Haanpää M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira
no. 155). [cited 19 Aug 2019]. Available from url: https://www.sign. D, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain
ac.uk/assets/sign155.pdf 2011;152(1):14-27.
12. Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and 29. Hara KW, Borchgrevink P. National guidelines for evaluating pain
managment of psoriasis and psoriatic arthritis in adults. Edinburgh: - Patients’ legal right to prioritised health care at multidisciplinary
SIGN; 2010. (SIGN publication no. 121). [cited 18 Oct 2013]. pain clinics in Norway implemented 2009. Scand J Pain
Available from url: http://www.sign.ac.uk/guidelines/fulltext/121/ 2010;1(1):60-3.
index.html
30. Hill JC, Whitehurst DG, Lewis M, Bryan S, Dunn KM, Foster NE, et
13. Merskey H, Bogduk N, (editors). Classification of chronic pain, al. Comparison of stratified primary care management for low
second edition. Seattle: IASP Press; 1994. back pain with current best practice (STarT Back): a randomised
controlled trial. Lancet 2011;378(9802):1560-71.
14. Birbaumer N, Lutzenberger W, Montoya P, Larbig W, Unertl K,
Töpfner S, et al. Effects of regional anesthesia on phantom limb 31. Lynch ME, Campbell F, Clark AJ, Dunbar MJ, Goldstein D, Peng P,
pain are mirrored in changes in cortical reorganization. J Neurosci et al. A systematic review of the effect of waiting for treatment for
1997;17(14):5503-8. chronic pain. Pain 2008;136(1-2):97-116.
15. Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer 32. Scottish Government. Better outcomes for older people: Framework
N, et al. Phantom-limb pain as a perceptual correlate of for joint services. 2005. [cited 18 Oct 2013]. Available from url: http://
cortical reorganization following arm amputation. Nature www.scotland.gov.uk/Publications/2005/05/13101338/13397
1995;375(6531):482-4.
33. Dobscha SK, Corson K, Perrin NA, Hanson GC, Leibowitz RQ, Doak
MN, et al. Collaborative care for chronic pain in primary care: a
cluster randomized trial. JAMA 2009;301(12):1242-52.
| 63
34. Becker A, Leonhardt C, Kochen MM, Keller S, Wegscheider K, Baum 51. Zech D, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World
E, et al. Effects of two guideline implementation strategies on Health Organization Guidelines for cancer pain relief: a 10-year
patient outcomes in primary care: a cluster randomized controlled prospective study. Pain 1995;63(1):65-76.
trial. Spine 2008;33(5):473-80.
52. Ventafridda V, Tamburini M, Caraceni A, De Conno F, Naldi F. A
35. Courtenay M, Carey N. The impact and effectiveness of nurse-led validation study of the WHO method for cancer pain relief. Cancer
care in the management of acute and chronic pain: a review of the 1987;59(4):850-6.
literature. J Clin Nurs 2008;17(15):2001-13.
53. World Health Organization. WHO’s pain relief ladder. [cited 18 Oct
36. Smith MY, Depue JD, Rini C. Computerized decision-support 2013]. Available from url: http://www.who.int/cancer/palliative/
systems for chronic pain management in primary care. Pain Med painladder/en/
2007;8(Suppl 3):S155-S66.
54. Maier C, Baron R, Tölle TR, Binder A, Birbaumer N, Birklein F, et al.
37. Manias E, Williams A. Managing pain in chronic kidney Quantitative sensory testing in the German Research Network
disease: patient participation in decision-making. J Adv Nurs on Neuropathic Pain (DFNS): somatosensory abnormalities in
2008;61(2):201-10. 1236 patients with different neuropathic pain syndromes. Pain
2010;150(3):439-50.
38. Alamo MM, Moral RR, Perula de Torres LA. Evaluation of a patient-
centred approach in generalized musculoskeletal chronic pain/ 55. Mogil JS. Pain genetics: past, present and future. Trends Genet
fibromyalgia patients in primary care. Patient Educ Couns 2012;28(6):258-66.
2002;48(1):23-31.
56. Dworkin RH, Turk DC, Basch E, Berger A, Cleeland C, Farrar JT, et
39. Stones RW, Lawrence WT, Selfe SA. Lasting impressions: influence al. Considerations for extrapolating evidence of acute and chronic
of the initial hospital consultation for chronic pelvic pain on pain analgesic efficacy. Pain 2011;152(8):1705-8.
dimensions of patient satisfaction at follow-up. J Psychosom Res
2006;60(2):163-7. 57. Chaparro LE, Wiffen PJ, Moore RA, Gilron I. Combination
pharmacotherapy for the treatment of neuropathic pain in adults.
40. Main CJ, Buchbinder R, Porcheret M, Foster N. Addressing patient Cochrane Database of Systematic Reviews 2012, Issue 7.
beliefs and expectations in the consultation. Best Pract Res Clin
Rheumatol 2010;24(2):219-25. 58. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Non-
steroidal anti-inflammatory drugs for low back pain. Cochrane
41. Cremeans-Smith JK, Stephens MAP, Franks MM, Martire LM, Druley Database of Systematic Reviews 2008, Issue 1.
JA, Wojno WC. Spouses’ and physicians’ perceptions of pain severity
in older women with osteoarthritis: Dyadic agreement and patients’ 59. Chou R, Huffman LH. Medications for acute and chronic low back
well-being. Pain 2003;106(1-2):27-34. pain: A review of the evidence for an American Pain Society/
American College of Physicians clinical practice guideline. Ann
42. Bieber C, Müller KG, Blumenstiel K, Hochlehnert A, Wilke S, Intern Med 2007;147(7):505-14.
Hartmann M, et al. A shared decision-making communication
training program for physicians treating fibromyalgia patients: 60. Kuijpers T, van Middelkoop M, Rubinstein SM, Ostelo R, Verhagen
effects of a randomized controlled trial. J Psychosom Res A, Koes BW, et al. A systematic review on the effectiveness of
2008;64(1):13-20. pharmacological interventions for chronic non-specific low-back
pain. Eur Spine J 2011;20(1):40-50.
43. Stomski NJ, Mackintosh S, Stanley M. Patient self-report measures
of chronic pain consultation measures: a systematic review. Clin J 61. Masso Gonzalez EL, Patrignani P, Tacconelli S, Garcia Rodriguez LA.
Pain 2010;26(3):235-43. Variability among nonsteroidal antiinflammatory drugs in risk of
upper gastrointestinal bleeding. Arthritis Rheum 2010;62(6):1592-
44. Du S, Yuan C, Xiao X, Chu J, Qiu Y, Qian H. Self-management 601.
programs for chronic musculoskeletal pain conditions: A
systematic review and meta-analysis. Patient Educ Couns 62. Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Bhala N,
2011;85(3):e299-e310. Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper
gastrointestinal effects of non-steroidal anti-inflammatory drugs:
45. Foster G, Taylor SJC, Eldridge S, Ramsay J, Griffiths CJ. Self- meta-analyses of individual participant data from randomised
management education programmes by lay leaders for people trials. Lancet 2013;382(9894):769-79.
with chronic conditions. Cochrane Database of Systematic Reviews
2007, Issue 4. 63. Jordan KM, Cameron JS, Snaith M, Zhang W, Doherty M, Seckl
J, et al. British Society for Rheumatology and British Health
46. Berman RL, Iris MA, Bode R, Drengenberg C. The effectiveness of Professionals in Rheumatology guideline for the management of
an online mind-body intervention for older adults with chronic gout. Rheumatology 2007;46(8):1372-4.
pain. J Pain 2009;10(1):68-79.
64. National Institute for Health and Clinical Excellence (NICE).
47. Carpenter KM, Stoner SA, Mundt JM, Stoelb B. An online self- Osteoarthritis: the care and management of osteoarthritis in adults.
help CBT intervention for chronic lower back pain. Clin J Pain London: NICE; 2008. (NICE guideline CG59). [cited 18 Oct 2013].
2012;28(1):14-22. Available from url: http://publications.nice.org.uk/osteoarthritis-
cg59
48. Chiauzzi E, Pujol LA, Wood M, Bond K, Black R, Yiu E, et al.
painACTION-back pain: a self-management website for people 65. National Institute for Health and Clinical Excellence (NICE).
with chronic back pain. Pain Med 2010;11(7):1044-58. Rheumatoid arthritis: national clinical guideline for management
and treatment in adults. London: NICE; 2009. [cited 18 Oct 2013].
49. Ruehlman LS, Karoly P, Enders C. A randomized controlled Available from url: http://publications.nice.org.uk/rheumatoid-
evaluation of an online chronic pain self management program. arthritis-cg79
Pain 2012;153(2):319-30.
50. Liddle SD, Gracey JH, Baxter GD. Advice for the management of
low back pain: a systematic review of randomised controlled trials.
Man Ther 2007;12(4):310-27.
64 |
References
66. Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan 83. Martell BA, O’Connor PG, Kerns RD, Becker WC, Morales KH, Kosten
P, et al. EULAR evidence based recommendations for gout. Part TR, et al. Systematic review: opioid treatment for chronic back pain:
II: Management. Report of a task force of the EULAR Standing prevalence, efficacy, and association with addiction. Ann Intern
Committee for International Clinical Studies Including Therapeutics Med 2007;146(2):116-27.
(ESCISIT) Ann Rheum Dis 2006;65(10):1312-24.
84. Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C,
67. Davies RA, Maher CG, Hancock MJ. A systematic review of et al. Long-term opioid management for chronic noncancer pain.
paracetamol for non-specific low back pain. Eur Spine J Cochrane Database of Systematic Reviews 2010, Issue 1.
2008;17(11):1423-30.
85. Steiner D, Munera C, Hale M, Ripa S, Landau C. Efficacy and safety
68. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells of buprenorphine transdermal system (BTDS) for chronic moderate
G. Acetaminophen for osteoarthritis. Cochrane Database of to severe low back pain: a randomized, double-blind study. J Pain
Systematic Reviews 2006, Issue 1. 2011;12(11):1163-73.
69. Doherty M, Hawkey C, Goulder M, Gibb I, Hill N, Aspley S, et al. 86. Yarlas A, Miller K, Wen W, Dain B, Lynch SY, Pergolizzi JV, et al. A
A randomised controlled trial of ibuprofen, paracetamol or a randomized, placebo-controlled study of the impact of the 7-day
combination tablet of ibuprofen/paracetamol in community- buprenorphine transdermal system on health-related quality of
derived people with knee pain. Ann Rheum Dis 2011;70(9):1534-41. life in opioid-naive patients with moderate-to-severe chronic low
back pain. J Pain 2013;14(1):14-23.
70. Richards BL, Whittle SL, Buchbinder R. Neuromodulators for pain
management in rheumatoid arthritis. Cochrane Database of 87. Haroutiunian S, McNicol ED, Lipman AG. Methadone for chronic
Systematic Reviews 2012, Issue 1. non-cancer pain in adults. Cochrane Database of Systematic
Reviews 2012, Issue 11.
71. Derry S, Massey T, Moore RA, McQuay HJ. Topical NSAIDS for chronic
musculoskeletal pain in adults. Cochrane Database of Systematic 88. Afilalo M, Etropolski MS, Kuperwasser B, Kelly K, Okamoto A, Van
Reviews 2012, Issue 4. Hove I, et al. Efficacy and safety of Tapentadol extended release
compared with oxycodone controlled release for the management
72. Derry S, Moore RA. Topical capsaicin (low concentration) for chronic of moderate to severe chronic pain related to osteoarthritis of the
neuropathic pain in adults. Cochrane Database of Systematic knee: a randomized, double-blind, placebo- and active-controlled
Reviews 2012, Issue 9. phase III study. Clin Drug Investig 2010;30(8):489-505.
73. De Silva V, El-Metwally A, Ernst E, Lewith G, Macfarlane GJ, Arthritis 89. Lange B, Kuperwasser B, Okamoto A, Steup A, Haufel T, Ashworth
Research UK Working Group on Complementary and Alternative J, et al. Efficacy and safety of tapentadol prolonged release
Medicines. Evidence for the efficacy of complementary and for chronic osteoarthritis pain and low back pain. Adv Ther
alternative medicines in the management of osteoarthritis: a 2010;27(6):381-99.
systematic review. Rheumatology 2011;50(5):911-20.
90. Furlan AD, Chaparro LE, Irvin E, Mailis-Gagnon A. A comparison
74. Derry S, Sven-Rice A, Cole P, Tan T, Moore RA. Topical capsaicin (high between enriched and nonenriched enrollment randomized
concentration) for chronic neuropathic pain in adults. Cochrane withdrawal trials of opioids for chronic noncancer pain. Pain Res
Database of Systematic Reviews 2013, Issue 2. Manag 2011;16(5):337-51.
75. Khaliq W, Alam S, Puri N. Topical lidocaine for the treatment of 91. Papaleontiou M, Henderson Jr CR, Turner BJ, Moore AA,
postherpetic neuralgia. Cochrane Database of Systematic Reviews Olkhovskaya Y, Amanfo L, et al. Outcomes associated with
2007, Issue 2. opioid use in the treatment of chronic noncancer pain in older
adults: A systematic review and meta-analysis. J Am Geriatr Soc
76. Fi n n e r u p N B, S i n d r u p S H , J e n s e n TS . Th e e v i d e n ce 2010;58(7):1353-69.
for pharmacological treatment of neuropathic pain. Pain
2010;150(3):573-81. 92. Devulder J, Jacobs A, Richarz U, Wiggett H. Impact of opioid rescue
medication for breakthrough pain on the efficacy and tolerability
77. Plested M, Budhia S, Gabriel Z. Pregabalin, the lidocaine plaster of long-acting opioids in patients with chronic non-malignant pain.
and duloxetine in patients with refractory neuropathic pain: a Br J Anaesth 2009;103(4):576-85.
systematic review. BMC Neurol 2010;10:116.
93. Annemans L. Pharmacoeconomic impact of adverse events of
78. Matthews P, Derry S, Moore RA, McQuay HJ. Topical rubefacients for long-term opioid treatment for the management of persistent
acute and chronic pain in adults. Cochrane Database of Systematic pain. Clin Drug Investig 2011;31(2):73-86.
94. Takkouche B, Montes-Martínez A, Gill SS, Etminan M. Psychotropic
79. Searle R, Hopkins PM. Pharmacogenomic variability and medications and the risk of fracture: a meta-analysis. Drug Saf
anaesthesia. Br J Anaesth 2009;103(1):14-25. 2007;30(2):171-84.
80. Bekkering GE, Soares-Weiser K, Reid K, Kessels AG, Dahan A, Treede 95. Fishbain DA, Cole B, Lewis J, Rosomoff HL, Rosomoff RS. What
RD, et al. Can morphine still be considered to be the standard for percentage of chronic nonmalignant pain patients exposed to
treating chronic pain? A systematic review including pair-wise and chronic opioid analgesic therapy develop abuse/addiction and/
network meta-analyses. Curr Med Res Opin 2011;27(7):1477-91. or aberrant drug-related behaviors? A structured evidence-based
review. Pain Med 2008;9(4):444-59.
81. Deshpande A, Furlan A, Mailis-Gagnon A, Atlas S, Turk D. Opioids for
chronic low-back pain. Cochrane Database of Systematic Reviews 96. Chou R, Fanciullo GJ, Fine PG, Miaskowski C, Passik SD, Portenoy RK.
2007, Issue 3. Opioids for chronic noncancer pain: prediction and identification
of aberrant drug-related behaviors: a review of the evidence for an
82. Manchikanti L, Ailinani H, Koyyalagunta D, Datta S, Singh V, Eriator
American Pain Society and American Academy of Pain Medicine
I, et al. A systematic review of randomized trials of long-term
clinical practice guideline. J Pain 2009;10(2):131-46.
opioid management for chronic non-cancer pain. Pain Physician
2011;14(2):91-121.
| 65
97. British Pain Society. Opioids for persistent pain: good practice. 114. Watson CPN, Gilron I, Sawynok J. A qualitative systematic review
London: British Pain Society; 2010. [cited 18 Oct 2013]. Available of head-to-head randomized controlled trials of oral analgesics in
from url: http://www.britishpainsociety.org/pub_professional. neuropathic pain. Pain Res Manag 2010;15(3):147-57.
htm#opioids
115. Mujakperuo HR, Watson M, Morrison R, Macfarlane T V.
98. Dunn KM, Saunders KW, Rutter CM, Banta-Green CJ, Merrill JO, Pharmacological interventions for pain in patients with
Sullivan MD, et al. Opioid prescriptions for chronic pain and temporomandibular disorders. Cochrane Database of Systematic
overdose: A cohort study. Ann Intern Med 2010;152(2):85-92. Reviews 2010, Issue 10.
99. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic 116. Urquhart DM, Hoving JL, Assendelft WWJJ, Roland M, Van Tulder
neuropathic pain and fibromyalgia in adults. Cochrane Database MW. Antidepressants for non-specific low back pain. Cochrane
of Systematic Reviews 2011, Issue 3. Database of Systematic Reviews 2008, Issue 1.
100. Kimos P, Biggs C, Mah J, Heo G, Rashiq S, Thie NM, et al. Analgesic 117. Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of
action of gabapentin on chronic pain in the masticatory muscles: fibromyalgia syndrome with antidepressants: a meta-analysis.
a randomized controlled trial. Pain 2007;127(1-2):151-60. JAMA 2009;301(2):198-209.
101. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for 118. Khoromi S, Cui L, Nackers L, Max MB. Morphine, nortriptyline and
acute and chronic pain in adults. Cochrane Database of Systematic their combination vs. placebo in patients with chronic lumbar root
Reviews 2009, Issue 3. pain. Pain 2007;130(1-2):66-75.
102. Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM. 119. Rintala DH, Holmes SA, Courtade D, Fiess RN, Tastard LV, Loubser PG.
Pregabalin reduces pain in patients with chronic pancreatitis in a Comparison of the effectiveness of amitriptyline and gabapentin
randomized, controlled trial. Gastroenterology 2011;141(2):536-43. on chronic neuropathic pain in persons with spinal cord injury.
Arch Phys Med Rehabil 2007;88(12):1547-60.
103. Zaccara G, Gangemi P, Perucca P, Specchio L. The adverse event
profile of pregabalin: a systematic review and meta-analysis of 120. Goldman RH, Stason WB, Park SK, Kim R, Mudgal S, Davis RB, et al.
randomized controlled trials. Epilepsia 2011;52(4):826-36. Low-dose amitriptyline for treatment of persistent arm pain due
to repetitive use. Pain 2010;149(1):117-23.
104. Stacey BR, Barrett JA, Whalen E, Phillips KF, Rowbotham MC.
Pregabalin for postherpetic neuralgia: placebo-controlled trial of 121. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for
fixed and flexible dosing regimens on allodynia and time to onset neuropathic pain and fibromyalgia in adults. Cochrane Database
of pain relief. J Pain 2008;9(11):1006-17. of Systematic Reviews 2012, Issue 12.
105. Pontari MA, Krieger JN, Litwin MS, White PC, Anderson RU, 122. Skljarevski V, Ossanna M, Liu-Seifert H, Zhang Q, Chappell A,
McNaughton-Collins M, et al. Pregabalin for the treatment of Iyengar S, et al. A double-blind, randomized trial of duloxetine
men with chronic prostatitis/chronic pelvic pain syndrome: a versus placebo in the management of chronic low back pain. Eur
randomized controlled trial. Arch Intern Med 2010;170(17):1586- J Neurol 2009;16(9):1041-8.
93.
123. Roskell NS, Beard SM, Zhao Y, Le TK. A meta-analysis of pain response
106. Simpson DM, Schifitto G, Clifford DB, Murphy TK, Durso-De Cruz E, in the treatment of fibromyalgia. Pain Pract 2011;11(6):516-27.
Glue P, et al. Pregabalin for painful HIV neuropathy: a randomized,
double-blind, placebo-controlled trial. Neurology 2010;74(5):413- 124. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful
20. neuropathy or chronic pain. Cochrane Database of Systematic
107. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for
acute and chronic pain in adults. Cochrane Database of Systematic 125. Hochberg MC, Wohlreich M, Gaynor P, Hanna S, Risser R. Clinically
Reviews 2011, Issue 1. relevant outcomes based on analysis of pooled data from 2 trials
of duloxetine in patients with knee osteoarthritis. J Rheumatol
108. Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium 2012;39(2):352-8.
valproate for neuropathic pain and fibromyalgia in adults.
Cochrane Database of Systematic Reviews 2011, Issue 10. 126. Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V,
Belenkov Y, et al. A double-blind, randomized, placebo-controlled
109. Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and study of the efficacy and safety of duloxetine for the treatment
fibromyalgia in adults. Cochrane Database of Systematic Reviews of chronic pain due to osteoarthritis of the knee. Pain Pract
2012, Issue 2. 2011;11(1):33-41.
110. Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic 127. Skljarevski V, Zhang S, Desaiah D, Alaka KJ, Palacios S, Miazgowski
pain. Cochrane Database of Systematic Reviews 2011, Issue 2. T, et al. Duloxetine versus placebo in patients with chronic low back
pain: a 12-week, fixed-dose, randomized, double-blind trial. J Pain
111. Birse F, Derry S, Moore RA. Phenytoin for neuropathic pain and 2010;11(12):1282-90.
fibromyalgia in adults. Cochrane Database of Systematic Reviews
2012, Issue 5. 128. Häuser W, Urrútia G, Tort S, Üçeyler N, Walitt B. Serotonin and
noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia syndrome.
112. Corrigan R, Derry S, Wiffen PJ, Moore RA. Clonazepam for Cochrane Database of Systematic Reviews 2013, Issue 1.
neuropathic pain and fibromyalgia in adults. Cochrane Database
of Systematic Reviews 2012, Issue 5. 129. Derry S, Gill D, Phillips T, Moore RA. Milnacipran for neuropathic
pain and fibromyalgia in adults. Cochrane Database of Systematic
113. Holbech JV, Otto M, Bach FW, Jensen TS, Sindrup SH. The Reviews 2012, Issue 3.
anticonvulsant levetiracetam for the treatment of pain in
polyneuropathy: a randomized, placebo-controlled, cross-over 130. Kroenke K, Bair MJ, Damush TM, Wu J, Hoke S, Sutherland J, et al.
trial. Eur J Pain 2011;15(6):608-14. Optimized antidepressant therapy and pain self-management in
primary care patients with depression and musculoskeletal pain:
a randomized controlled trial. JAMA 2009;301(20):2099-110.
66 |
References
131. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 148. Aggarwal VR, Lovell K, Peters S, Javidi H, Joughin A, Goldthorpe
1965;150(3699):971-9. J. Psychosocial interventions for the management of chronic
orofacial pain. Cochrane Database of Systematic Reviews 2011,
132. Von Korff M, Simon G. The relationship between pain and Issue 11.
depression. Br J Psychiatry Suppl 1996;30:101-8.
149. Monticone M, Baiardi P, Vanti C, Ferrari S, Nava T, Montironi C, et
133. Engel G. The need for a new medical model: A challenge for al. Chronic neck pain and treatment of cognitive and behavioural
biomedicine. Science 1977;196(4286):129-36. factors: results of a randomised controlled clinical trial. Eur Spine
J 2012;21(8):1558-66.
134. Ravenek MJ, Hughes ID, Ivanovich N, Tyrer K, Desrochers C, Klinger
L, et al. A systematic review of multidisciplinary outcomes in the 150. Sharpe L, Schrieber L. A blind randomized controlled trial of
management of chronic low back pain. Work 2010;35(3):349-67. cognitive versus behavioral versus cognitive-behavioral therapy
for patients with rheumatoid arthritis. Psychother Psychosom
135. van Middelkoop M, Rubinstein SM, Kuijpers T, Verhagen AP, Ostelo 2012;81(3):145-52.
R, Koes BW, et al. A systematic review on the effectiveness of
physical and rehabilitation interventions for chronic non-specific 151. McBeth J, Prescott G, Scotland G, Lovell K, Keeley P, Hannaford
low back pain. Eur Spine J 2011;20(1):19-39. P, et al. Cognitive behavior therapy, exercise, or both for treating
chronic widespread pain. Arch Intern Med 2012;172(1):48-57.
136. van Geen JW, Edelaar MJ, Janssen M, van Eijk JT. The long-term
effect of multidisciplinary back training: a systematic review. Spine 152. Buhrman M, Nilsson-Ihrfeldt E, Jannert M, Strom L, Andersson G.
2007;32(2):249-55. Guided internet-based cognitive behavioural treatment for chronic
back pain reduces pain catastrophizing: a randomized controlled
137. Scascighini L, Toma V, Dober-Spielmann S, Sprott H. Multidisciplinary trial. J Rehabil Med 2011;43(6):500-5.
treatment for chronic pain: a systematic review of interventions
and outcomes. Rheumatology 2008;47(5):670-8. 153. Thorn BE, Day MA, Burns J, Kuhajda MC, Gaskins SW, Sweeney
K, et al. Randomized trial of group cognitive behavioral therapy
138. Van Koulil S, Van Lankveld W, Kraaimaat FW, Van Helmond T, Vedder compared with a pain education control for low-literacy rural
A, Van Hoorn H, et al. Tailored cognitive-behavioral therapy and people with chronic pain. Pain 2011;152(12):2710-20.
exercise training for high-risk patients with fibromyalgia. Arthritis
Care Res 2010;62(10):1377-85. 154. Veehof MM, Oskam MJ, Schreurs KM, Bohlmeijer ET. Acceptance-
based interventions for the treatment of chronic pain: a systematic
139. Heutink M, Post MWM, Bongers-Janssen HMH, Dijkstra CA, review and meta-analysis. Pain 2011;152(3):533-42.
Snoek GJ, Spijkerman DCM, et al. The CONECSI trial: Results of
a randomized controlled trial of a multidisciplinary cognitive 155. Schmidt S, Grossman P, Schwarzer B, Jena S, Naumann J, Walach
behavioral program for coping with chronic neuropathic pain after H. Treating fibromyalgia with mindfulness-based stress reduction:
spinal cord injury. Pain 2012;153(1):120-8. results from a 3-armed randomized controlled trial. Pain
2011;152(2):361-9.
140. Brox JI, Storheim K, Grotle M, Tveito TH, Indahl A, Eriksen HR.
Systematic review of back schools, brief education, and fear- 156. Wong SYS, Chan FWK, Wong RLP, Chu MC, Kitty Lam YY, Mercer
avoidance training for chronic low back pain. Spine J 2008;8(6):948- SW, et al. Comparing the effectiveness of mindfulness-based stress
58. reduction and multidisciplinary intervention programs for chronic
pain: A randomized comparative trial. Clin J Pain 2011;27(8):724-34.
141. Engers AJ, Jellema P, Wensing M, van der Windt DAWM, Grol R,
van Tulder MW. Individual patient education for low back pain. 157. Chiesa A, Serretti A. Mindfulness-based interventions for chronic
Cochrane Database of Systematic Reviews 2008, Issue 1. pain: a systematic review of the evidence. J Altern Complement
Med 2011;17(1):83-93.
142. Clarke CL, Ryan CG, Martin DJ. Pain neurophysiology education
for the management of individuals with chronic low back pain: 158. Wetherell JL, Afari N, Rutledge T, Sorrell JT, Stoddard JA, Petkus AJ,
systematic review and meta-analysis. Man Ther 2011;16(6):544-9. et al. A randomized, controlled trial of acceptance and commitment
therapy and cognitive-behavioral therapy for chronic pain. Pain
143. Roland M, Waddell G, Moffett JK, Burton K, Main C, Cantrell T. The 2011;152(9):2098-107.
Back Book. London: The Stationery Office; 2002.
159. Rubinstein SM, van Middelkoop M, Assendelft WJ, de Boer MR, van
144. Gallagher L, McAuley J, Moseley GL. A randomized-controlled Tulder MW. Spinal manipulative therapy for chronic low-back pain.
trial of using a book of metaphors to reconceptualize pain and Cochrane Database of Systematic Reviews 2011, Issue 2.
decrease catastrophizing in people with chronic pain. Clin J Pain
2013;29(1):20-5. 160. Furlan AD, Imamura M, Dryden T, Irvin E. Massage for low-back
pain. Cochrane Database of Systematic Reviews 2008, Issue 4.
145. Henschke N, Ostelo RWJG, van Tulder MW, Vlaeyen JWS, Morley S,
Assendelft WJJ, et al. Behavioural treatment for chronic low-back 161. Miller J, Gross A, D’Sylva J, Burnie SJ, Goldsmith CH, Graham N, et
pain. Cochrane Database of Systematic Reviews 2010, Issue 7. al. Manual therapy and exercise for neck pain: a systematic review.
Man Ther 2010;15(4):334-54.
146. Glombiewski JA, Hartwich-Tersek J, Rief W. Two psychological
interventions are effective in severely disabled, chronic back 162. Gross A, Miller J, D’Sylva J, Burnie SJ, Goldsmith CH, Graham N, et
pain patients: a randomised controlled trial. Int J Behav Med al. Manipulation or mobilisation for neck pain. Cochrane Database
2010;17(2):97-107. of Systematic Reviews 2010, Issue 1.
147. Hoffman BM, Papas RK, Chatkoff DK, Kerns RD. Meta-analysis of 163. Busch AJ, Schachter CL, Overend TJ, Peloso PM, Barber KA. Exercise for
psychological interventions for chronic low back pain. Health fibromyalgia: a systematic review. J Rheumatol 2008;35(6):1130-44.
Psychol 2007;26(1):1-9.
| 67
164. Slade SC, Keating JL. Unloaded movement facilitation exercise 181. Rubinstein SM, van Middelkoop M, Kuijpers T, Ostelo R, Verhagen
compared to no exercise or alternative therapy on outcomes for AP, de Boer MR, et al. A systematic review on the effectiveness of
people with nonspecific chronic low back pain: a systematic review. complementary and alternative medicine for chronic non-specific
J Manipulative Physiol Ther 2007;30(4):301-11. low-back pain. Eur Spine J 2010;19(8):1213-28.
165. May S, Johnson R. Stabilisation exercises for low back pain: a 182. Vickers AJ, Cronin AM, Maschino AC, Lewith G, Macpherson H,
systematic review. Physiotherapy 2008;94(3):179-89. Foster NE, et al. Acupuncture for chronic pain: individual patient
data meta-analysis. Arch Intern Med 2012;172(19):1444-53.
166. Hendrick P, Te Wake AM, Tikkisetty AS, Wulff L, Yap C, Milosavljevic
S. The effectiveness of walking as an intervention for low back pain: 183. Manheimer E, Cheng K, Linde K, Lao L, Yoo J, Wieland S, et al.
a systematic review. Eur Spine J 2010;19(10):1613-20. Acupuncture for peripheral joint osteoarthritis. Cochrane Database
of Systematic Reviews 2010, Issue 1.
167. Hall A, Maher C, Latimer J, Ferreira M. The effectiveness of Tai Chi
for chronic musculoskeletal pain conditions: a systematic review 184. Reinhold T, Witt CM, Jena S, Brinkhaus B, Willich SN. Quality of life
and meta-analysis. Arthritis Rheum 2009;61(6):717-24. and cost-effectiveness of acupuncture treatment in patients with
osteoarthritis pain. Eur J Health Econ 2008;9(3):209-19.
168. Lim EC, Poh RL, Low AY, Wong WP. Effects of Pilates-based exercises
on pain and disability in individuals with persistent nonspecific 185. Posadzki P, Zhang J, Lee MS, Ernst E. Acupuncture for chronic
low back pain: a systematic review with meta-analysis. J Orthop nonbacterial prostatitis/chronic pelvic pain syndrome: a systematic
Sports Phys Ther 2011;41(2):70-80. review. J Androl 2012;33(1):15-21.
169. Bussing A, Ostermann T, Ludtke R, Michalsen A. Effects of yoga 186. Asher GN, Jonas DE, Coeytaux RR, Reilly AC, Loh YL, Motsinger-Reif
interventions on pain and pain-associated disability: a meta- AA, et al. Auriculotherapy for pain management: a systematic
analysis. J Pain 2012;13(1):1-9. review and meta-analysis of randomized controlled trials. J Altern
Complement Med 2010;16(10):1097-108.
170. Waller B, Lambeck J, Daly D. Therapeutic aquatic exercise in the
treatment of low back pain: a systematic review. Clin Rehabil 187. Arthritis Research UK. Practitioner-based complementary and
2009;23(1):3-14. alternative therapies for the treatment of rheumatoid arthritis,
osteoarthritis, fibromyalgia and low back pain. Chesterfield:
171. Jordan JL, Holden MA, Mason EE, Foster NE. Interventions to Arthritis Research UK; 2013. [cited 18 Oct 2013]. Available from
improve adherence to exercise for chronic musculoskeletal pain url: http://www.arthritisresearchuk.org/arthritis-information/
in adults. Cochrane Database of Systematic Reviews 2010, Issue 1. complementary-and-alternative-medicines/complementary-and-
alternative-therapies.aspx
172. Teasell RW, McClure JA, Walton D, Pretty J, Salter K, Meyer M, et al.
A research synthesis of therapeutic interventions for whiplash- 188. Arthritis Research UK. Complementary and alternative medicines
associated disorder (WAD): part 4 - noninvasive interventions for for the treatment of rheumatoid arthritis, osteoarthritis and
chronic WAD. Pain Res Manag 2010;15(5):313-22. fibromyalgia. Chesterfield: Arthritis Research UK; 2012. [cited 18
Oct 2013]. Available from url: http://www.arthritisresearchuk.org/
173. Ferreira ML, Smeets RJ, Kamper SJ, Ferreira PH, Machado LA. Can we arthritis-information/complementary-and-alternative-medicines/
explain heterogeneity among randomized clinical trials of exercise complementary-and-alternative-medicines.aspx
for chronic back pain? A meta-regression analysis of randomized
controlled trials. Phys Ther 2010;90(10):1383-403. 189. Cui X, Trinh K, Wang YJ. Chinese herbal medicine for chronic neck
pain due to cervical degenerative disc disease. Cochrane Database
174. Clarke JA, van Tulder MW, Blomberg SE, de Vet HC, van der Heijden of Systematic Reviews 2010, Issue 1.
GJ, Bronfort G, et al. Traction for low-back pain with or without
sciatica. Cochrane Database of Systematic Reviews 2007, Issue 2. 190. Cepeda MS, Carr DB, Lau J, Alvarez H. Music for pain relief. Cochrane
Database of Systematic Reviews 2006, Issue 2.
175. Nnoaham KE, Kumbang J. Transcutaneous electrical nerve
stimulation (TENS) for chronic pain. Cochrane Database of 191. Sesti F, Capozzolo T, Pietropolli A, Collalti M, Bollea MR, Piccione E.
Systematic Reviews 2008, Issue 3. Dietary therapy: A new strategy for management of chronic pelvic
pain. Nutr Res Rev 2011;24(1):31-8.
176. Dubinsky RM, Miyasaki J. Assessment: efficacy of transcutaneous
electric nerve stimulation in the treatment of pain in neurologic 192. Hagen KB, Byfuglien MG, Falzon L, Olsen SU, Smedslund G. Dietary
disorders (an evidence-based review): report of the Therapeutics interventions for rheumatoid arthritis. Cochrane Database of
and Technology Assessment Subcommittee of the American Systematic Reviews 2009, Issue 1.
Academy of Neurology. Neurology 2010;74(2):173-6.
193. Straube S, Derry S, Moore RA, McQuay HJ. Vitamin D for the
177. Khadilkar A, Odebiyi DO, Brosseau L, Wells GA. Transcutaneous treatment of chronic painful conditions in adults. Cochrane
electrical nerve stimulation (TENS) versus placebo for chronic Database of Systematic Reviews 2010, Issue 1.
low-back pain. Cochrane Database of Systematic Reviews 2008,
Issue 4. 194. Szczurko O, Cooley K, Busse JW, Seely D, Bernhardt B, Guyatt GH,
et al. Naturopathic care for chronic low back pain: a randomized
178. Kroeling P, Gross A, Goldsmith CH, Burnie SJ, Haines T, Graham N, et trial. PLoS ONE 2007;2(9):e919.
al. Electrotherapy for neck pain. Cochrane Database of Systematic
Reviews 2009, Issue 4. 195. British Pain Society. Pain Assessment and Management Pathways.
[cited 18 Oct 2013]. Available from url: http://bps.mapofmedicine.
179. Yousefi-Nooraie R, Schonstein E, Heidari K, Rashidian A, Pennick com/evidence/bps/index.html
V, Akbari-Kamrani M, et al. Low level laser therapy for nonspecific
low-back pain. Cochrane Database of Systematic Reviews 2008, 196. Haanpää ML, Backonja MM, Bennett MI, Bouhassira D, Cruccu G,
Issue 2. Hansson PT, et al. Assessment of neuropathic pain in primary care.
Am J Med 2009;122(10 Suppl):S13-21.
180. Hopton A, MacPherson, H. Acupuncture for chronic pain: is
acupuncture more than an effective placebo? A systematic review
of pooled data from meta-analyses. Pain Pract 2010;10(2):94-102.
68 |
References
197. Berterame S, Erthal J, Thomas J, Fellner S, Vosse B, Clare P, et al. 214. Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S,
Use of and barriers to access to opioid analgesics: a worldwide, Turk DC. Opioids compared to placebo or other treatments for
regional, and national study. Lancet 2016;387(10028):1644-56. chronic low-back pain. Cochrane Database of Systematic Reviews
2013, Issue 8.
198. Schuchat A, Houry D, Guy GP. New data on opioid use and
prescribing in the united states. JAMA 2017;318(5):425-6. 215. Santos J, Alarcao J, Fareleira F, Vaz-Carneiro A, Costa J. Tapentadol
for chronic musculoskeletal pain in adults. Cochrane Database of
199. Seth P, Scholl L, Rudd RA, Bacon S. Overdose deaths involving Systematic Reviews 2015, Issue 5.
opioids, cocaine, and psychostimulants - United States, 2015–2016.
MMWR Morb Mortal Wkly Rep 2018;67(12):349-58. 216. Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith
ES, et al. Effect of opioid vs nonopioid medications on pain-
200. Curtis HJ, Croker R, Walker AJ, Richards GC, Quinlan J, Goldacre B. related function in patients with chronic back pain or hip or knee
Opioid prescribing trends and geographical variation in England, osteoarthritis pain: the SPACE randomized clinical trial. JAMA
1998-2018: a retrospective database study. Lancet Psychiatry 2018;319(9):872-82.
2019;6(2):140-50.
217 Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R,
201. Torrance N, Mansoor R, Wang H, Gilbert S, Macfarlane GJ, Serpell M, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in
et al. Association of opioid prescribing practices with chronic pain adults: a systematic review and meta-analysis. Lancet Neurol
and benzodiazepine co-prescription: a primary care data linkage 2015;14(2):162-73.
study. Br J Anaesth 2018;120(6):1345-55.
218. Cooper TE, Chen J, Wiffen PJ, Derry S, Carr DB, Aldington D, et
202. International Association for the Study of Pain (IASP). IASP al. Morphine for chronic neuropathic pain in adults. Cochrane
Statement on Opioids. [cited 18 Jun 2019]. Available from url: http:// Database of Systematic Reviews 2017, Issue 5.
www.iasp-pain.org/Advocacy/Content.aspx?ItemNumber=7194
219. Duehmke RM, Derry S, Wiffen PJ, Bell RF, Aldington D, Moore RA.
203. Neuman MD, Bateman BT, Wunsch H. Inappropriate opioid Tramadol for neuropathic pain in adults. Cochrane Database of
prescription after surgery. Lancet 2019;393(10180):1547-57. Systematic Reviews 2017, Issue 6.
204. Medicines Complete. BNF: Guidance on prescribing. [cited 27 Jun 220. Gaskell H, Derry S, Stannard C, Moore RA. Oxycodone for
2019]. Available from url: https://www.medicinescomplete.com/#/ neuropathic pain in adults. Cochrane Database of Systematic
content/bnf/PHP97234 Reviews 2016, Issue 7.
205. Dean L. Codeine therapy and CYP2D6 genotype. [cited 18 Jun 221. McNicol ED, Ferguson MC, Schumann R. Methadone for
2019]. Available from url: https://www.ncbi.nlm.nih.gov/books/ neuropathic pain in adults. Cochrane Database of Systematic
NBK100662/ Reviews 2017, Issue 5.
206. Meske DS, Lawal OD, Elder H, Langberg V, Paillard F, Katz N. Efficacy 222. Stannard C, Gaskell H, Derry S, Aldington D, Cole P, Cooper TE,
of opioids versus placebo in chronic pain: A systematic review and et al. Hydromorphone for neuropathic pain in adults. Cochrane
meta-analysis of enriched enrollment randomized withdrawal Database of Systematic Reviews 2016, Issue 5.
trials. J Pain Res 2018;11:923-34
223. Wiffen PJ, Derry S, Moore RA, Stannard C, Aldington D, Cole P, et al.
207. Busse JW, Wang L, Kamaleldin M, Craigie S, Riva JJ, Montoya L, et Buprenorphine for neuropathic pain in adults. Cochrane Database
al. Opioids for chronic noncancer pain: a systematic review and of Systematic Reviews 2015, Issue 9.
meta-analysis. JAMA 2018;320(23):2448.
224. Hegmann KT, Weiss MS, Bowden K, Branco F, DuBrueler K, Els C,
208. Chou R, Deyo R, Devine B, Hansen R, Sullivan S, Jarvik JG, et al. The et al. ACOEM practice guidelines: opioids for treatment of acute,
effectiveness and risks of long-term opioid treatment of chronic subacute, chronic, and postoperative pain. J Occup Environ Med
pain. Evid Rep Technol Assess (Full Rep) 2014(218):1-219. 2014;56(12):e143-59.
209. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, 225. NHS Scotland, Effective Prescribing and Therapeutics Branch.
et al. The effectiveness and risks of long-term opioid therapy for Chronic pain prescribing strategy. [cited 18 Jun 2019]. Available
chronic pain: a systematic review for a National Institutes of Health from url: https://www.therapeutics.scot.nhs.uk/pain/
Pathways to Prevention Workshop. Annals of Internal Medicine
2015;162(4):276-86. 226. Busse JW, Craigie S, Juurlink DN, Buckley DN, Wang L, Couban RJ,
et al. Guideline for opioid therapy and chronic noncancer pain.
210. Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing CMAJ 2017;189(18):E659-E66.
opioids for chronic pain--United States, 2016. JAMA
2016;315(15):1624-45. 227. Scottish Government and NHS Scotland. Quality prescribing for
chronic pain: A guide for improvement 2018-2021. [cited 18 Jun
211. Els C, Jackson Tanya D, Hagtvedt R, Kunyk D, Sonnenberg B, Lappi 2019]. Available from url: https://www.therapeutics.scot.nhs.uk/
Vernon G, et al. High-dose opioids for chronic non-cancer pain: an wp-content/uploads/2018/03/Strategy-Chronic-Pain-Quality-
overview of Cochrane Reviews. Cochrane Database of Systematic Prescribing-for-Chronic-Pain-2018.pdf
Reviews 2017, issue 10.
228. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes
212. Wolff RF, Aune D, Truyers C, Hernandez AV, Misso K, Riemsma R, DN. Rates of opioid misuse, abuse, and addiction in chronic pain:
et al. Systematic review of efficacy and safety of buprenorphine a systematic review and data synthesis. Pain 2015;156(4):569-76.
versus fentanyl or morphine in patients with chronic moderate to
severe pain. Curr Med Res Opin 2012;28(5):833-45. 229. Higgins C, Smith BH, Matthews K. Incidence of iatrogenic opioid
dependence or abuse in patients with pain who were exposed to
213. Abdel Shaheed C, Maher CG, Williams KA, Day R, McLachlan opioid analgesic therapy: a systematic review and meta-analysis.
AJ. Efficacy, tolerability, and dose-dependent effects of opioid Br J Anaesth 2018;120(6):1335-44.
analgesics for low back pain: a systematic review and meta-analysis.
JAMA Intern Med 2016;176(7):958-68.
| 69
230. Minozzi S, Amato L, Davoli M. Development of dependence

following treatment with opioid analgesics for pain relief: a
systematic review. Addiction 2013;108(4):688-98.
231. Lawrence R, Mogford D, Colvin L. Systematic review to determine

which validated measurement tools can be used to assess risk
of problematic analgesic use in patients with chronic pain. Br J
Anaesth 2017;119(6):1092-109.
232. Birthi P, Nagar VR, Nickerson R, Sloan PA. Hypogonadism associated

with long-term opioid therapy: A systematic review. J Opioid
Manag 2015;11(3):255-78.
233. Zhao S, Deng T, Luo L, Wang J, Li E, Liu L, et al. Association between

opioid use and risk of erectile dysfunction: a systematic review and
meta-analysis. J Sex Med 2017;14(10):1209-19.
234. Wersocki E, Bedson J, Chen Y, LeResche L, Dunn KM. Comprehensive

systematic review of long-term opioids in women with chronic
noncancer pain and associated reproductive dysfunction
(hypothalamic-pituitary-gonadal axis disruption). Pain
2017;158(1):8-16.
235. Huang L, Zhou J-G, Zhang Y, Wang F, Wang Y, Liu D-H, et al.
Opioid-induced constipation relief from fixed-ratio combination
prolonged-release oxycodone/naloxone compared with
oxycodone and morphine for chronic nonmalignant pain: a
systematic review and meta-analysis of randomized controlled
trials. J Pain Symptom Manage 2017;54(5):737-48.e3.
70 |
ISBN 978 1 909103 16 0
www.sign.ac.uk
www.healthcareimprovementscotland.org
Edinburgh Office | Gyle Square |1 South Gyle Crescent | Edinburgh | EH12 9EB
Telephone 0131 623 4300 Fax 0131 623 4299
Glasgow Office | Delta House | 50 West Nile Street | Glasgow | G1 2NP

Telephone 0141 225 6999 Fax 0141 248 3776
The Healthcare Environment Inspectorate, the Scottish Health Council, the Scottish Health Technologies Group, the Scottish
Intercollegiate Guidelines Network (SIGN) and the Scottish Medicines Consortium are key components of our organisation.

SIGN 136 - Management of Chronic Pain

Uploaded by

Copyright:

Available Formats

SIGN 136 - Management of Chronic Pain

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

SIGN 136 - Management of Chronic Pain

Uploaded by

Copyright:

Available Formats

SIGN 136 • Management of chronic pain

A national clinical guideline First published December 2013

3 Non-analytic studies, eg case reports, case series

Management of chronic pain

First published December 2013

Scottish Intercollegiate Guidelines Network

First published December 2013

ISBN 978 1 909103 16 0

This document is licensed under the Creative Commons Attribution-Noncommercial-NoDerivatives 4.0

1.2 REMIT OF THE GUIDELINE

1.2.1 OVERALL OBJECTIVES

1.2.2 TARGET USERS OF THE GUIDELINE

1.2.3 SUMMARY OF UPDATES TO THE GUIDELINE, BY SECTION

5.3 Opioids Completely revised (2019)

1.4 REPORTING IN PAIN TRIALS

1.5 STATEMENT OF INTENT

1.5.1 PATIENT VERSION

1.5.2 PRESCRIBING OF LICENSED MEDICINES OUTWITH THEIR MARKETING AUTHORISATION

2.1 ASSESSMENT AND PLANNING OF CARE

2.2 SUPPORTED SELF MANAGEMENT

2.3 PHARMACOLOGICAL MANAGEMENT

2.4 PSYCHOLOGICALLY BASED INTERVENTIONS

2.5 PHYSICAL THERAPIES

3 Assessment and planning of care

A pathway for assessment can be found in Annex 2.

3.2 TIMING OF INTERVENTION

3.3 CARE MANAGEMENT

3.4 PATIENT-PROFESSIONAL INTERACTION

4 Supported self management

for these studies varied, but overall improvements were small.

Sources of further information for patients can be found in Section 10.

Reproduced with permission from the World Health Organization

5.2 NON-OPIOID ANALGESICS (SIMPLE AND TOPICAL)

5.2.1 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

with osteoporosis and chronic low back pain (SMD 0.3).59

5.2.4 TOPICAL NSAIDS

5.2.5 TOPICAL CAPSAICIN

5.2.6 TOPICAL LIDOCAINE

5.2.7 TOPICAL RUBEFACIENTS

5.3.3 ADVERSE EFFECTS

5.4 ANTIEPILEPSY DRUGS

5.4.4 OTHER ANTIEPILEPSY DRUGS

5.5.1 TRICYCLIC ANTIDEPRESSANTS

5.5.2 SEROTONIN NOREPINEPHRINE RE-UPTAKE INHIBITOR

5.5.3 SELECTIVE SEROTONIN RE-UPTAKE INHIBITOR

5.5.4 CHRONIC PAIN WITH CONCOMITANT DEPRESSION

5.6 COMBINATION THERAPIES

6 Psychologically based interventions

6.1 MULTIDISCIPLINARY PAIN MANAGEMENT PROGRAMMES

improvements in the multidisciplinary treatment group compared to controls.136

6.2 UNIDISCIPLINARY EDUCATION

6.2.1 BRIEF EDUCATION

disability in either the short or the long term. 140,141

6.2.2 PAIN NEUROPHYSIOLOGY EDUCATION

6.3 BEHAVIOURAL THERAPIES

6.3.1 RESPONDENT BEHAVIOURAL THERAPIES

6.3.2 OPERANT BEHAVIOURAL THERAPIES

6.4 COGNITIVE BEHAVIOURAL THERAPY

SIGN 136 • Management of chronic pain

a. multidisciplinary pain management programmes based on biopsychosocial principles

e. third wave psychological treatments: acceptance and commitment