International Journal of

Environmental Research
and Public Health

Review
Effect of Multi-Modal Therapies for Kinesiophobia
Caused by Musculoskeletal Disorders: A Systematic
Review and Meta-Analysis
Yining Xu 1 , Yang Song 2,3 , Dong Sun 1, *, Gusztáv Fekete 4 and Yaodong Gu 1, *
1 Faculty of Sports Science, Ningbo University, Ningbo 315211, China; [email protected]
2 Doctoral School of Safety and Security Sciences, Obuda University, 1034 Budapest, Hungary;
[email protected]
3 Faculty of Engineering, University of Szeged, 6724 Szeged, Hungary
4 Savaria Institute of Technology, Eötvös Loránd University, 9700 Szombathely, Hungary; [email protected]
* Correspondence: [email protected] (D.S.); [email protected] (Y.G.)




Received: 18 October 2020; Accepted: 4 December 2020; Published: 16 December 2020


Abstract: This systematic review and meta-analysis aimed to identify the effect of multi-modal
therapies that combined physical and psychological therapies for kinesiophobia caused by
musculoskeletal disorders compared with uni-modal therapy of only phycological therapy
or psychological therapy. The search terms and their logical connector were as following:
(1) “kinesiophobia” at the title or abstract; and (2) “randomized” OR “randomized” at title or
abstract; not (3) ”design” OR “protocol” at the title. They were typed into the databases of Medline
(EBSCO), PubMed, and Ovid, following the different input rules of these databases. The eligibility
criteria were: (1) Adults with musculoskeletal disorders or illness as patients; (2) Multi-modal
therapies combined physical and psychological therapy as interventions; (3) Uni-modal therapy of
only physical or psychological therapy as a comparison; (4) The scores of the 17-items version of
the Tampa Scale of Kinesiophobia as the outcome; (5) Randomized controlled trials as study design.
As a result, 12 studies were included with a statistically significant polled effect of 6.99 (95% CI
4.59 to 9.38). Despite a large heterogeneity within studies, multi-modal therapies might be more
effective in reducing kinesiophobia than the unimodal of only physical or psychological therapy
both in the total and subdivision analysis. The effect might decrease with age. What’s more, this
review’s mathematical methods were feasible by taking test-retest reliability of the Tampa Scale of
Kinesiophobia into consideration.

Keywords: kinesiophobia; pain; multi-modal; psychological measure; Tampa scale

1. Introduction
Musculoskeletal disorders and the following pain were common in most people’s daily life [1],
and the musculoskeletal pain caused by musculoskeletal disorders was the second most common
cause of disability [2]. Many established factors, such as physical, biological, cognitive, behavioral,
social, and occupation, were correlated with the pain following musculoskeletal disorders [1,3,4].
Fear was considered to be an explanation of why pain and associated outcomes such as disability
persist once the body injury had healed [5,6], and the fear-avoidance model of pain was one of the
frameworks which could explain the development and persistence of the pain and disability following
a musculoskeletal injury [7,8]. According to this model, people with a trait tend to have fear and
catastrophic thoughts in response to pain were more at risk of developing chronic musculoskeletal pain
after an injury than people who did not have this tendency [6,8]. These people over-reacted in response
to actual or potential threats, developing avoidance behaviors to prevent a new injury/re-injury [6]. Fear

Int. J. Environ. Res. Public Health 2020, 17, 9439; doi:10.3390/ijerph17249439 www.mdpi.com/journal/ijerph
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in relation to pain had been described with various conceptual definitions, among which pain-related
fear, fear-avoidance beliefs, fear of movement, and kinesiophobia were the most commonly used [9].
Kinesiophobia was one of the most commonly used conceptual definitions which could describe
fear in relation to pain [10]. Kinesiophobia (also known as the fear of movement) was defined as
an excessive, irrational, and debilitating fear to carry out a physical movement due to a feeling of
vulnerability to a painful injury or re-injury [10]. It could be acquired through a direct aversive
experience such as pain and trauma or through social learning such as observation and instruction [11].
Kinesiophobia had been associated with pain, disability, and quality of daily life to some extent [12].
The prevalence of kinesiophobia in chronic pain was from 50% to 70% [13,14].
The objective of rehabilitation is to recover physical exercises’ performance, regain the capacity
of daily activities, and restore social functions. In recent years, studies on the rehabilitation of
musculoskeletal disorders had begun to focus on the fear in relation to pain [15,16]. The fear in relation
to pain would cause people to produce fear-avoidance and had a negative effect on their quality of life.
Therefore, not only the rehabilitation at the physical level but also the rehabilitation at the psychological
level should be paid attention to [17–20]. At the same time, as mentioned above, kinesiophobia could
be acquired through many different ways (e.g., personal experience, social learning) [11], therapies
combined multi-modal from both psychological and physical perspectives had become increasingly
popular [15,21,22]. However, at present, only a few studies focus on the advantage of multi-modal
therapies over uni-modal therapies, and most of the studies on the rehabilitation of musculoskeletal
disorders were limited to specific musculoskeletal disorders. There was a lack of high-quality evidence
from the macro-perspective. To answer this question, the terms “physical therapy” and “psychological
therapy” should be defined in this review at first.
In this review, the terms “physical therapy” and “psychological therapy” were defined as follows.
“Physical therapy” was the therapy included: (1) exercise/training session or advice with a private plan;
(2) passive physical therapies such as usual care; (3) treatments provided by professional therapists or
medical staff without any psychological education. It should be emphasized that exercise/training
advice without a private plan, waiting lists and interventions without any control, such as keeping
normal daily life, would be excluded.
“Psychological therapy” was the therapy include (1) psychological education; (2)
cognition-behavior therapy; (3) perceptive stimulation in non-injured body areas such as virtual
reality equipment, laser, and relaxation; (4) therapeutic milieu involves interpersonal communication
such as group session and feedback session. It should be emphasized that if the doctor-patient
communication in the intervention involved only an explanation of the treatment or only guidance of
exercise or only supervision in training, the intervention wouldn’t be regarded as psychological therapy.
Moreover, a quantitative indicator was required to assess the fear of movement, and there was not
a specific tool to assess fear of movement directly [9]. The term “kinesiophobia” would be used. People
with kinesiophobia would change their movements to avoid pain and adjust their motor behaviors [12].
The processing of pain and pain-related information in people with musculoskeletal disorders could
be related to how kinesiophobia was perceived [23]. Therefore, a greater degree of kinesiophobia
predicted greater levels of fear of pain and a great inclination to avoid physical movements [24].
Kinesiophobia could be measured by the Tampa Scale of Kinesiophobia (TSK) [25]. Since the
Tampa Scale of Kinesiophobia had good validity in the quantization of kinesiophobia, the change of
TSK scores would reflect the effect of therapy and be taken as a comparative indicator of therapy effect
to some extent [26,27]. In the original version of the Tampa Scale of Kinesiophobia, participants would
be asked to respond to how much they agreed with each of the 17 items, and the ratings available were:
(1) disagree; (2) partially disagree; (3) partially agree; (4) strongly agree. The score of each item varies
from 1–4 or 0–3. The responses were summed, and the generated score, which ranges from 17 to 68 or
from 0 to 51 [13,25]. However, the TSK scores were usually reported as a secondary outcome, and that
there was a limited number of studies that focus on the treatments for kinesiophobia. It made that a
special study search strategy, information extraction, and data processing methods need to be applied.
Int. J. Environ. Res. Public Health 2020, 17, 9439 3 of 22

This systematic review and meta-analysis aimed to identify the effect of multi-modal therapies,
which combined physical and psychological therapies following the definition mentioned above, for
kinesiphobia caused by musculoskeletal disorders compared with uni-modal therapies of an only
physical or only psychological therapy that followed the definitions mentioned above.

2. Methods

2.1. Protocol and Registration

This review was conducted in accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement (Registration number: CRD42020218384) [28].

2.2. Eligibility and Exclusion Criteria And Rationale of PICOS

Studies were included in this review if they met the following eligibility criteria: (1) Patients
should be adults with musculoskeletal disorders or illness. What should be emphasized was that
the patients with the injuries and their following pain, which cause by surgery and other diseases
of tissues and organs, would be excluded; (2) Intervention should be multi-modal therapy, which
combined physical and psychological therapy. The definitions of physical therapy and psychological
therapy were given in the introduction. For example, a cognitive-behavioral group intervention
contained a skill training plan would be regarded as multi-modal therapy; (3) The comparison was
multi-modal therapies versus uni-modal therapies. The uni-modal therapy should be physical therapy
or psychological therapy, the definitions of which were given in the introduction. For example, a
supervised home exercise with a given plan would be regarded as a uni-modal therapy from a physical
perspective; (4) Outcomes would be scores of the 17-items version of the Tampa Scale of Kinesiophobia;
(5) Randomized controlled trials; (6) Date and Language: published in English from inception to
September 2020.
The 17-items Tampa Scale of Kinesiophobia had been demonstrated predictive and constructed
validity as well as excellent test-retest reliability (0.64–0.91) and internal consistency (0.70–0.81).
What should be paid attention to was that there were some shorten versions of the Tampa Scale of
Kinesiophobia, such as TSK-11, TSK-13, and the Tampa Scale of Kinesiophobia for particular injuries.
All of these versions demonstrated high validities, reliabilities, and consistencies as well. To ensure the
consistency of results and reduce the heterogeneity, only the 17-items version would be chosen as this
review’s outcome, and the 17-items version whose scores ranged from 0 to 3 would be converted to 1
to 4.
Studies would be excluded if they met the following eligibility criteria: (1) Healthy people,
children, and teenagers; (2) pain caused by trauma, burns, or surgery; (3) other versions of the Tampa
Scale of Kinesiophobia; (4) lack of origin scores of the Tampa Scale of Kinesiophobia.

2.3. Search and Study Selection

The search terms and their logical connector were as following: (1) “kinesiophobia” at the title or
abstract; and (2) “randomized” OR “randomized” at title or abstract; not (3) “design” OR “protocol” at
the title. They were typed into the databases of Medline (EBSCO), PubMed, and Ovid, following the
different input rules of these databases.
In the database PubMed, the search term”(kinesiophobia[Title/Abstract]) AND ((randomized) or
(randomised)[Title/Abstract]) NOT ((design) or (protocol)[Title])” was used, then the results would
be limited at “randomized controlled trials”. In the database Medline (EBSCO), the search term “AB
kinesiophobia and AB (randomized or randomised) NOT TI (design or protocol)” was used, and the
range of search would be fixed in Cochrane Central Register of Trials, Medline with Full Text, and
CINAHL. In the database Ovid, “All Resources” would be chosen, and the search term “(kinesiophobia
and (randomized or randomised) .ab not (design or protocol) .at” was used with the tool “Multi-Field
Int. J. Environ. Res. Public Health 2020, 17, 9439 4 of 22

Search”, and the language would be limited in English. All the results would be downloaded and
imported into EndNote X9 for further screening.
With the help of the functions “deduplication” and “searching in library” of EndNote X9, the
duplicated and ineligible studied would be screened.
A unified method and standard of study search and Selection were used, in which the two authors
(Y.X. and Y.S.) searched the study in turn, independently. The figures and tables for information would
be made after the two authors verified their results finally. An independent arbitrator (D.S) resolved
any discrepancies in data extraction.

2.4. Data Extraction and Management

A unified method and standard of data extraction were used, in which the two authors (Y.X. and
Y.S.) extracted the information in turn, independently. The figures and tables for information would be
made after the two authors verified their data finally. An independent arbitrator (D.S.) resolved any
discrepancies in data extraction.
The following data are collected. (1) The versions of The Tampa Scale of Kinesiophobia and
their test-retest reliabilities, which could be searched in the references of these studies, or be inferred
from the nationalities of the participants; (2) The origin scores of the Tampa Scale of Kinesiophobia at
baselines and different follow-up times; (3) The mean age of participants which would be combined by
statistical Formulas; (4) The types of musculoskeletal pain; (5) The duration of interventions.
All the scores of the Tampa Scale of Kinesiophobia would be converted to the form of MEAN
(SD). If an included study reported the Tampa Scale of Kinesiophobia scores of different follow-up
times or had more than one trial arm, each different follow-up times and trial arm would be treated as
a separate trial [29].
It should be paid attention that some original data of included studies should be revised to
unify and standardize. The corrected mean differences and standard deviations of the Tampa Scale
of Kinesiophobia scores of the baselines and the follow-up times could be calculated by the basic
statistical Formulas (1) and (2) (The number 1 means the baseline and the number 2 represents the
follow-ups). The correlation coefficient R was the test-retest reliability or the internal consistency
coefficient of the Tampa Scale of Kinesiophobia, which was used in the included studies. Different
language versions of the Tampa Scale had different test-retest reliabilities. If a study didn’t report
the version of the Tampa Scale of Kinesiophobia, the rest-retest reliability would be inferred from the
participants’ nationalities or references of the study:

MD = MD1 − MD2 , (1)

q
SD = SD21 + SD22 − 2R·SD1· SD2 , (2)

Since the scores of the Tampa Scale of Kinesiophobia were in the same units, the standardized
mean difference was not chosen to illustrate the pooled effect. The software RevMan5.3 was used to
analyze the combined effect, and the random effect model (REM) was chosen. All the total and subtotal
results would be shown in the forest plots made by RevMan5.3.
The size of heterogeneity would be tested by two indexes, one of which was I2 , a qualitative
and descriptive index showing the inconsistency of the included studies, and the other was Tau2 , an
quantitative and analytical index showing the true difference. The statistic Q, which was equal to the
statistic Chi2 calculated by the RevMan5.3, and the confidence intervals of T2 and I2 , could explain
whether the result has the true heterogeneity.
The prediction intervals of all the statistics mentioned above, which combines the estimation of
the mean effect with the variance of the true effect and approximate the actual dispersion of the true
effect as the number of studies tend to infinity, were calculated as well.
Int. J. Environ. Res. Public Health 2020, 17, 9439 5 of 22

2.5. Risk of Bias and Quality of Evidence

A unified assessment method and standard of the risk of bias were used, in which the two authors
(Y.X. and Y.S.) assessed each study in turn, independently. The figures for information would be
made after the two authors verified their data finally. An independent arbitrator (D.S.) resolved any
discrepancies in the assessment of the risk of bias. The Cochrane Collaboration’s tool was used to
assess the risk of bias [30]. The trials’ quality was assessed and graded independently by two authors
according to the criteria described in The Cochrane Handbook. And the risk of bias graph and the risk
of bias summary graph would be made by RevMan5.3.
A Funnel plot based on the calculation of standard mean difference (SMD) was used in this review
to describe the existence of bias across studies. The analysis of bias risk was based on the following
model assumptions. (1) Studies with large sample sizes were more likely to be published; (2) Studies
on medium-sized samples were easily omitted; (3) Studies with small sample sizes were most likely to
be missed.
The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system,
which would be made by the software GRADEprofiler (Version 3.2.2), was used to illustrate the quality
of evidence [31].

2.6. Addition Analysis

2.6.1. Subgroup Analysis

If the heterogeneity of the pooled effect were large, a subgroup analysis would be necessary
to evaluate the source of heterogeneity and the influencing factors of the effect. The heterogeneity
between the studies might come from different types of musculoskeletal pain, different follow-up
times, and the different mean age of the participants, and different durations of treatments. Therefore,
the subgroup analysis would be conducted from the following aspects: (1) Types of musculoskeletal
pain; (2) Follow-up times; (3) Mean of the participants; (4) Duration of Treatments; (5) Different control
group interventions. All the continuous variables would be divided into several subgroups for analysis.
However, the subgroup analysis might not explain the source of heterogeneity. For a certain covariate,
a further meta-regression would be made if there were enough studies.

2.6.2. Meta-Regression
Meta-Regression, whose results could explain the correlation of different subgroup deviations
and the pooled effect, would be made by the software STATA® 14. Following the meta-regression
principles, the restricted maximum likelihood (REML) was used in meta-regression, and the regression
coefficient is expressed in exponential form (exp). Moreover, the Monte Carlo Method was used to
correct the P-value to verify the existence of the type I error. The times of calculation was set to 5000.

2.6.3. Statistical Power

Generally, the statistical power should be analyzed before primary studies or a meta-analysis.
However, to verify the rationality of this review’s mathematical method, the statistical power of every
primary study, meta-analysis, and heterogeneity analysis would be calculated. Generally, although
researchers often wanted the statistical power of their study to be at least 80%, a single primary
study’s statistical power was usually low. The statistical power of studies from medicine, psychology,
education, and other fields of science were generally less than 80% and less than 50% when testing for
low effects. Since a meta-analysis had a larger sample size than any included study, it usually had
higher statistical power. In this review, each included studies’ statistical power, the meta-analysis, the
subgroup analysis, and the heterogeneity test were calculated.
Int. J. Environ. Res. Public Health 2020, 17, 9439 6 of 22

3. Results

3.1. Study Selection, Information, and Original Data

In the database PubMed, by the search term “(kinesiophobia[Title/Abstract]) AND ((randomized)
or (randomised)[Title/Abstract]) NOT ((design) or (protocol)[Title])”, and the limitation of “randomized
controlled trials”, 55 studies had been screened out. In the database Medline (EBSCO), by the search
term “AB kinesiophobia and AB (randomized or randomised) NOT TI (design or protocol)”, and the
range of “Cochrane Central Register of Trials, Medline with Full Text, and CINAHL”, 507 studies had
been screened out. In the database Ovid, by the search term “(kinesiophobia and (randomized or
randomised) .ab not (design or protocol) .at” typed in the tool “Multi-Field Search”, and the limitation
of English, 480 studies had been screened out. All the results would be downloaded and imported into
EndNote X9 for further screening.
After deduplication and applying the exclusion criteria, 12 studies [32–43] of the total 1042 studies
were included for analysis. The flow diagram could be seen in Figure 1. Based on the information of
all the full texts included, the result of data collection and a summary measure of each included study
could be seen in Tables 1 and 2.

Figure 1. The PRISMA 2009 flow diagram of search and study selection.
Int. J. Environ. Res. Public Health 2020, 17, 9439 7 of 22

Table 1. The result of data collection.

Study Design Characteristics of Participants

Version of TSK Multi-Modal Therapy Group Uni-Modal Therapy Group
Study
Duration of Duration of Mean Age Type of Pain
Language R Intervention Intervention N Intervention Intervention N
(Weeks) (Weeks)
Gardner 2019 Education + Patient-led goal Standardised advice to Chronic Low-back
English 0.820 8 37 8 38 44.51
[34] setting intervention exercise with a plan Pian
Nambi Isokinetic training with Chronic Low-back
English 0.820 Virtual reality training 4 20 4 20 23.00
2020-Arm1 [43] a plan Pian
Nambi Conventional training Chronic Low-back
English 0.820 Virtual reality training 4 20 4 20 23.25
2020-Arm2 with a plan Pian
Manual therapy + Supervised Manual therapy +
Saracoglu Chronic Low-back
Turkish 0.806 home exercise + Pain neuroscience 4 20 Supervised home 4 19 40.50
2020-Arm1 [40] Pian
education exercise
Manual therapy + Supervised
Saracoglu Supervised home Chronic Low-back
Turkish 0.806 home exercise + Pain neuroscience 4 20 4 18 39.94
2020-Arm2 exercise Pian
education
Gustavsson 2006
Swedish 0.910 Relaxation treatment 7 13 Treatment as usual 20 16 37.48 Chronic Neck Pain
[32]
Javdaneh 2020 Cognitive functional therapy + Scapular exercise with a
Persian 0.920 6 24 6 24 29.50 Chronic Neck Pain
[42] Scapular exercise plan
Physical training + Specific
Ris 2016 [36] English 0.820 16 101 Pain education 16 99 45.15 Chronic Neck Pain
exercises + Pain education
Cervical kinematic training + Cervical kinematic
Bahat 2015 [33] Dutch 0.780 5 16 5 16 40.88 Chronic Neck Pain
Interactive Virtual Reality training training with a plan
Cognitive-behavioural
Tompson 2016 Progressive neck
English 0.820 physiotherapy + Progressive neck 24 29 24 28 47.53 Chronic Neck Pain
[37] exercise
exercise
Traditional Non-special
Yilmza 2017 [41] Turkish 0.806 Virtual walking therapy 2 22 2 22 25.14
Physiotherapy Low-back Pain
Cognitive-behavioral group
Helminen 2015 Ordinary general Knee Osteoarthritis
Finnish 0.890 intervention contains skill training 6 55 6 56 63.64
[39] practitioner care Pain
plan
Usual care by Upper extremity
Treatment combined physical and
Meijer 2006 [35] Dutch 0.780 2 20 occupational health 2 14 38.14 musculoskeletal
psychological sessions
services disorders
Immersive Virtual Reality +
Gulsen 2020 [38] Turkish 0.806 8 8 Exercise with a plan 8 8 42.50 Fibromyalgia
Exercise
Total 405 398
Average 0.829 7.1 8.1 38.7
Int. J. Environ. Res. Public Health 2020, 17, 9439 8 of 22

Table 2. The converted scores of TSK by the form of MEAN (SD).

Baseline (T0) Follow-Up Times (T1) Follow-Up Times (T2) Follow-Up Times (T3)
Study Group
TSK + N0 TSK + Duration N1 TSK + Duration N2 TSK + Duration N3
36.60 29.30 30.00 31.20
OG 37 8 37 16 37 48 37
(7.50) (6.90) (5.30) (7.90)
Gardner 2019 [34]
39.90 39.40 39.30 37.30
CG 38 8 38 16 38 48 38
(9.30) (8.30) (8.10) (8.00)
57.52 26.43 20.12
OG 20 4 20 24 19
Nambi 2020-Arm1 (4.80) (3.50) (2.50)
[43] 58.11 27.54 21.21
CG 20 4 20 24 20
(4.50) (3.80) (2.40)
57.52 26.43 20.12
OG 20 4 20 24 19
(4.80) (3.50) (2.50)
Nambi 2020-Arm2
57.93 46.21 38.64
CG 20 4 20 24 19
(4.30) (4.10) (3.90)
44.35 35.55 35.19
OG 20 4 20 6
Saracoglu 2020-Arm1 (4.30) (5.75) (3.99)
[40] 45.10 41.63 42.21
CG 19 4 19 6
(4.45) (5.23) (5.04)
44.35 35.55 35.19
OG 20 4 20 6
(4.30) (5.75) (3.99)
Saracoglu 2020-Arm2
45.55 44.94 44.88
CG 18 4 18 6
(4.10) (4.70) (5.10)
26.00 27.00 29.00
OG 13 7 13 20 13
(7.46) (5.22) (5.22)
Gustavsson 2006 [32]
29.50 32.00 30.00
CG 16 7 16 20 16
(1.67) (0.00) (2.00)
50.00 21.00
OG 24 6 24
(5.23) (5.22)
Javdaneh 2020 [42]
49.00 30.00
CG 24 6 24
(4.78) (3.55)
Int. J. Environ. Res. Public Health 2020, 17, 9439 9 of 22

Table 2. Cont.

Baseline (T0) Follow-Up Times (T1) Follow-Up Times (T2) Follow-Up Times (T3)
Study Group
TSK + N0 TSK + Duration N1 TSK + Duration N2 TSK + Duration N3
37.80 36.57
OG 101 16 101
(0.69) (4.50)
Ris 2016 [36]
37.70 37.49
CG 99 16 99
(0.71) (4.50)
32.75 30.13 31.23
OG 16 5 16 12 14
(6.80) (5.70) (6.50)
Bahat 2015 [33]
30.38 28.64 30.00
CG 16 5 14 12 12
(5.80) (9.90) (5.90)
36.70 32.00
OG 29 24 29
(7.10) (14.11)
Tompson 2016 [37]
33.60 33.80
CG 28 24 28
(9.00) (15.04)
43.72 29.56
OG 22 2 22
(4.32) (4.04)
Yilmza 2017 [41]
40.36 38.70
CG 22 2 22
(5.61) (5.44)
35.00 33.00
OG 55 6 55
(1.25) (1.05)
Helminen 2015 [39]
33.30 32.50
CG 56 6 56
(1.35) (1.33)
38.90 29.10 25.80 26.40
OG 20 8 20 24 20 48 20
(1.51) (1.54) (2.65) (1.90)
Meijer 2006 [35]
40.91 41.00 39.90 40.40
CG 14 8 14 24 14 48 14
(1.81) (1.68) (3.16) (2.65)
49.00 35.00
OG 8 8 8
(4.44) (7.41)
Gulsen 2020 [38]
47.00 40.00
CG 8 8 8
(7.22) (5.37)
+: Mean (SD); TSK: Tampa scale of Kinesiophobia; OG: Operate group (Multi-modal therapy); CG: Control group (Uni-modal therapy).
Int. J. Environ. Res. Public Health 2020, 17, 9439 10 of 22

3.2. Risk of Bias

The result of the criteria for judging the risk of bias in the “Risk of bias assessment tool” would be
shown in Figure 2a,b. A funnel plot of the included studies, as in Figure 2c, illustrated the risk of bias
across studies and showed the relationship between the sample size and the effect. And the result of
the assessment of evidence quality, which was made by following the GRADE, would be put into the
Supplementary File (Figure S1).

Figure 2. Results of risk of bias analysis: (a) Risk of bias summary; (b) Graph of risk of bias; (c) Funnel
plot of included studies.

3.3. Data Extraction and Management

In the comparison of multi-modal interventions and uni-modal interventions with the scores of
TSK as the outcome, all the 12 included studies were divided into 24 independent trials. The result of
original data processing was shown in Table 3, and the forest plots of the pooled effect, which were
calculated by RevMan5.3, were shown in Figure 3.
Int. J. Environ. Res. Public Health 2020, 17, 9439 11 of 22

Table 3. The result of original data processing.

Duration of Follow-Up Mean Experiment Control

Study Intervention Times Age MD SD N MD SD N
(Weeks) (Weeks)
Gardner 2019 (1) [34] 8 8 44.51 7.30 4.36 37 0.50 5.37 38
Gardner 2019 (2) 8 16 44.51 6.60 4.38 37 0.60 5.34 38
Gardner 2019 (3) 8 48 44.51 5.40 4.64 37 2.60 5.34 38
Nambi 2020-Arm1 (1) [43] 4 4 23.00 31.09 2.78 20 24.34 2.58 20
Nambi 2020-Arm1 (2) 4 24 23.00 37.40 3.18 20 30.67 2.88 20
Nambi 2020-Arm2 (1) 4 4 23.25 31.09 2.78 20 11.72 2.53 20
Nambi 2020-Arm2 (2) 4 24 23.25 37.40 3.18 20 19.29 2.63 20
Saracoglu 2020-Arm1 (1)
4 4 40.50 8.80 3.42 20 3.47 3.10 19
[40]
Saracoglu 2020-Arm1 (2) 4 6 40.50 9.16 2.60 20 2.89 3.01 19
Saracoglu 2020-Arm2 (1) 4 4 39.94 8.80 3.42 20 0.61 2.78 18
Saracoglu 2020-Arm2 (2) 4 6 39.94 9.16 2.60 20 0.67 3.02 18
Gustavsson 2006 (1) [32] 7 7 37.48 -1.00 3.47 13 -2.50 1.67 16
Gustavsson 2006 (2) 7 20 37.48 -3.00 3.47 13 -0.50 0.84 16
Javdaneh 2020 [42] 6 6 29.50 29.00 2.09 24 19.00 2.06 24
Ris 2016 [36] 16 16 45.15 1.23 3.95 101 0.21 3.93 99
Bahat 2015 (1) [33] 5 5 40.88 2.13 4.20 16 1.50 8.30 14
Bahat 2015 (2) 5 12 40.88 1.23 6.80 14 0.92 4.50 12
Tompson 2016 [37] 24 24 47.53 4.70 9.23 29 -0.20 9.23 28
Yilmza 2017 [41] 2 2 25.14 14.26 2.62 22 1.66 3.45 22
Helminen 2015 [39] 6 6 63.64 2.00 0.57 55 0.50 0.63 56
Meijer 2006 (1) [35] 2 8 38.14 9.80 1.01 20 -0.10 3.26 14
Meijer 2006 (2) 2 24 38.14 13.10 1.75 20 1.00 2.77 14
Meijer 2006 (3) 2 48 38.14 12.50 1.20 20 0.50 2.86 14
Gulsen 2020 [38] 8 8 42.50 14.00 4.65 8 7.00 4.30 8
MD: Mean Difference; SD: Standard Deviation; N: Sample Size.

Figure 3. The forest plot of the comparison between the multi-modal therapies and uni-modal therapies.

The Q statistic of the meta-analysis of all included studies (equal to Chi2 ), T2 , I2 and their 95%
confidence intervals and prediction intervals of the comparisons’ effect could be seen in Table 4.

Table 4. The result of heterogeneity test of all included studies.

Prediction
Statistics of Heterogeneity Test 95% CI of T2 95% CI of I2
Intervals
df Q I2 Tau2 LL UL LL UL LL UL
23 1549.94 99% 34.21 3.37 4.09 0.87 0.89 0.00 * 19.33
df: Degree of freedom; LL: Lower limit; UL: Upper limit; *: the true value is less than 0.
Int. J. Environ. Res. Public Health 2020, 17, 9439 12 of 22

3.4. Additional Analysis

3.4.1. Subgroup Analysis

The calculation of subgroup analysis was based on the randomized effect model by RevMan5.3.
According to the result of the subgroup analysis, there was a large heterogeneity within studies
in subgroup analysis since the I2 of each subgroup analysis was large, meaning that the different
subgroups may not be the sources of the heterogeneity within the included studies, and it was necessary
to do a meta-regression.
According to the characteristics of participants and design of the included studies which might
affect the effectiveness of therapies, there were five subdivisions in the subgroup analysis: (1) different
types of pain, which included chronic low-back pain, chronic neck pain, and non-special low-back
pain; (2) different ranges of participants’ mean age which included 20 to 30, 30 to 40, and more than
40 years old; (3) different durations of treatments which included 0 to 3 weeks, 4 to 6 weeks, 7 to 9
weeks and more than 9 weeks; (4) different follow-up times which included 0 to 12 weeks, 13 to 24
weeks and more than 24 weeks; (5) different types of uni-modal interventions in control groups, which
include passive physical therapy, active exercise, and only psychological education (following the
hypothesis that there were different effects between passive physical therapies, active exercise, and
psychological-only interventions). The indexes of heterogeneity and their 95% confidence intervals
were shown in Table 5, and all the forest plots of the subdivisions would be shown in Figure 4.

Figure 4. Cont.
Int. J. Environ. Res. Public Health 2020, 17, 9439 13 of 22

Figure 4. Cont.
Int. J. Environ. Res. Public Health 2020, 17, 9439 14 of 22

Figure 4. The forest plot of the subgroup analysis: (a) The subdivisions of different types of pain;
(b) The subdivisions of different ranges of participants’ mean age; (c) The subdivisions of different
durations of treatments; (d) The subdivisions of different follow-up times; (e) The subdivisions of
different types of physical therapy in control groups.
Int. J. Environ. Res. Public Health 2020, 17, 9439 15 of 22

Table 5. The result of heterogeneity test of subgroup analysis.

Prediction
Outcome Statistics of Heterogeneity Test 95% CI of T2 95% CI of I2
Subgroups Intervals
Subdivision
df Q I2 Tau2 LL UL LL UL LL UL
CLBP 10 323.8 97% 29.62 3.63 5.37 79% 85% 0.00 * 21.29
Types of CNP 6 181.84 97% 28.79 3.39 5.70 78% 85% 0.00 * 16.59
Pain UEMD 2 4.02 50% 0.73 0* 1.18 0% * 62% 0.00 * 26.55
20–30 5 49.24 90% 2.71 0.39 1.02 56% 77% 6.14 18.38
Mean Age of
30–40 6 127.78 95% 5.34 0.70 1.28 73% 83% 0.14 14.10
Participants
40+ 8 63.73 87% 0.61 0.10 0.24 53% 73% 1.01 7.05
0–3 weeks 3 5.31 44% 0.58 0* 0.98 0% * 57% 7.03 16.29
Duration of 4–6 weeks 11 1065.22 99% 45.64 3.73 4.74 89% 91% 0.00 * 23.12
Treatments 7–9 weeks 5 54.64 91% 13.68 1.95 4.86 59% 78% 0.00 * 14.31
9+ weeks 1 2.39 58% 4.38 0* 6.85 0% 69% N/N N/N
0–12 weeks 14 965.81 99% 35.78 3.40 4.34 87% 89% 0.00* 20.28
Follow-up 13–24 weeks 6 380.24 98% 53.32 4.90 7.19 85% 89% 0.00 * 25.90
Times 24+ weeks 1 37.07 97% 13.05 1.02 3.15 74% 90% N/N N/N

Physical Active
12 327.26 96% 27.47 3.63 5.34 78% 84% 0.00 * 19.82
Therapy in Exercise
Control Passive
6 546.14 99% 39.00 3.13 4.36 88% 91% 0.00 * 23.27
Groups Therapy
df: Degree of freedom; LL: Lower limit; UL: Upper limit; *: the true value is less than 0; CNP: Chronic neck pain;
CLBP: Chronic low-back pain; UEMD: Upper extremity musculoskeletal disorders; N/N: when df = 1, the t-value
could not be calculated so that the prediction intervals could not be estimated as well.

3.4.2. Meta-Regression
The large heterogeneity within the included studies made it necessary to do a meta-regression.
The meta-regression made using STATA® 12 (StataCorp LLC, College Station, TX, USA), and the
results can be seen in Figure 5 and Table 6.
The result of the meta-regression calculation for the covariate “follow-up times” showed that the
proportion of the residual variation due to heterogeneity, which could be represented by the statistic
“I-squared_res”, was 99.58%. It meant that only 0.42% of the residual variation could be explained by
between-study variance. And the result of the meta-regression calculation of the covariate “mean age
of participants” showed that the proportion of the residual variation due to heterogeneity, which could
be represented by the statistic “I2 residual ” (I-squared_res), was 96.11%. It meant that only 3.89% of the
residual variation could be explained by between-study variance. The proportion of the heterogeneity
could be explained by between-study variance, which could be represented by the statistic “adjusted
R2 ” (Adj R-squared), which was 33.10%. The result of the meta-regression calculation of the covariate
“duration of treatments” showed that the proportion of the residual variation due to heterogeneity,
which could be represented by the statistic “I2 residual ” (I-squared_res), was 98.38%. It meant that
only 1.62% of the residual variation could be explained by between-study variance. The proportion
of the heterogeneity could be explained by between-study variance, which could be represented
by the statistic “adjusted R2 ” (Adj R-squared), which was 14.46%. Lastly, the result of the Monte
Carlo Permutation Test for Single Covariate of Meta-regression, the adjusted p-value changed from
0.139 to 0.008 to 1000 within the covariate “duration of treatments”, “mean age of participants”, and
“follow-up times”, indicating that there might not be the type I error existing within the included
studies. The bubble chats of the results of the three covariates in the meta-regression.
Int. J. Environ. Res. Public Health 2020, 17, 9439 16 of 22

Figure 5. The bubble chats of the results of the three covariates in the meta-regression: (a) The duration
of treatments; (b) Mean age of participants; (c) Follow-up times.

Table 6. Meta-regression result: The follow-up times and the SMD of effect.

Meta-Regression
Results Covariate
Duration of Mean Age of Follow-Up Times
Item Index
Treatments Participants (Week)
Number of obs N 24 24 24
REML estimate of
Tau2 24.39 19.08 29.86
between-study variance
% residual variation due to
I-squared_res 98.38% 96.11% 99.58%
heterogeneity
Proportion of between-study
Adj R-squared 14.46% 33.10% −4.74%
variance explained
Statistical Significance P-value 0.052 0.002 0.963
Monte Carlo Permutation Test Adjusted P-value 0.139 0.008 1.000
Int. J. Environ. Res. Public Health 2020, 17, 9439 17 of 22

3.4.3. Statistical Power

According to the result shown in Table 7, the meta-analysis’s statistical power was higher than
any included study. Moreover, the statistical power of the heterogeneity analysis was less than that of
the pooled effect because of the interactions between the covariables. The result was consistent with
the previous hypothesis.

Table 7. The result of statistical power test of all included studies and meta-analysis.

Statistical Statistical Power

Statistical Power
Study Subdivisions Subgroups Power of Effect of Heterogeneity
of Study
Combination Test
Gardner 2019 (1) [34] 13.45% CLBP 100.00% 51.76%
Gardner 2019 (2) 18.34% Types of Pain CNP 48.92% 39.09%
Gardner 2019 (3) 8.15% UEMD 100.00% 22.36%
Nambi 2020-Arm1 (1) [43] 5.62% 0–12 weeks 100.00% 61.90%
Follow-up
Nambi 2020-Arm1 (2) 11.75% 13–24 weeks 99.66% 39.09%
times
Nambi 2020-Arm2 (1) 17.54% 24+ weeks 48.16% 16.58%
Nambi 2020-Arm2 (2) 5.82% 20–30 100.00% 35.41%
Mean Age of
Saracoglu 2020-Arm1 (1)
14.54% Participants 30–40 99.99% 39.09%
[40]
Saracoglu 2020-Arm1 (2) 6.13% 40+ 99.42% 45.79%
Saracoglu 2020-Arm2 (1) 5.61% Physical Active Exercise 100.00% 57.10%
Therapy in Passive
Saracoglu 2020-Arm2 (2) 21.80% Control Groups 100.00% 39.09%
Therapy
Gustavsson 2006 (1) [32] 19.81% 0–3 weeks 100.00% 27.16%
Gustavsson 2006 (2) 11.61% Duration of 4–6 weeks 100.00% 54.51%
Javdaneh 2020 [42] 56.06% Treatments 7–9 weeks 55.56% 35.41%
Ris 2016 [36] 64.57% 9+ weeks 14.78% 16.58%
Bahat 2015 (1) [33] 67.83%
Bahat 2015 (2) 9.84%
Tompson 2016 [37] 10.11%
Yilmza 2017 [41] 7.36%
Helminen 2015 [39] 9.19% Total 100.00% 77.95%
Meijer 2006 (1) [35] 23.34%
Meijer 2006 (2) 11.27%
Meijer 2006 (3) 52.40%
Gulsen 2020 [38] 27.89%
CNP: Chronic neck pain; CLBP: Chronic low-back pain; UEMD: Upper extremity musculoskeletal disorders.

4. Discussion
In this review, the fear-avoidance model of pain was used to explain the fear of physical movement
following musculoskeletal disorders, and the clinic term “Kinesiophobia” was used to define and
describe fear in relation to pain. Kinesiophobia could be acquired through personal experience or social
learning and could be measured by the Tampa Scale of Kinesiophobia (TSK). Studies used the scores of
TSK-17 as one of the outcomes and compared therapies combined multi-modal from both psychological
and physical perspectives with therapies in uni-modal were included in this review to summarize the
evidence that might support the application of multi-modal therapies for musculoskeletal disorders
and the following pain.
Although a considerable heterogeneity within the included studies, the pooled effect was positive
with a statistical significance, indicating that multi-modal therapies had an advantage over uni-modal
therapies. High-quality evidence reported that a long-lasting multi-modal program was superior to
the exercise program in reducing disability, fear-avoidance beliefs and pain, and enhancing the quality
of life of patients with different kinds of pain [15]. The effects were clinically tangible and lasted for at
least one year after the intervention ended [15,20,22].
The results of the subgroup analysis in the subdivision of different types of pain, which was
showed in Figure 4a indicated that the multi-modal therapies were more used in the treatments for
chronic pain in the people’s trunk, especially in the neck and low back. This result was consistent with
the previous fear-avoidance model about the fear of pain, which was that the experience of chronic,
ongoing pain tends to become fear of pain [6,8]. What’s more, multi-modal therapies combined
Int. J. Environ. Res. Public Health 2020, 17, 9439 18 of 22

with physical therapies and psychological therapies had an advantage over therapies from a physical
perspective, no matter the physical therapy was passive or active, as was showed in Figure 4e. Therefore,
it was necessary to add psychological therapies in the treatments of chronic pain. A similar effect
was found in studies that compared passive and active treatments for neck-shoulder pain and used
the Visual Pain Scale (VAS) as an outcome measure [44]. Simultaneously, the age of participants, the
duration of treatments, and the different follow-up times might affect the results. Within these factors,
the participants’ age was more likely to be taken into consideration since the pooled effects showed a
decreasing trend with the increase of age in Figure 4b. According to the previous study results, older
people were more often had a pain of longer duration, more frequently and of more complexity, felt
more disabled, received more pain treatments and had more health problems, and often used passive
coping for pain [45]. The influence of different durations of treatments seemed unclear, as was in
Figure 4c. Perhaps there were few studies comparing different durations of treatments for pain or
kinesiophobia, and each treatment protocol had a different optimal duration. It might result in low
homogeneity among studies and poor goodness of fit of regression equations, as shown in Table 6.
At last, the pooled effects at different follow-up times seemed stale, as was in Figure 4d, indicating that
the effects of multi-modal therapies might clinically tangible and lasted for a long time [15,46].
According to the meta-regression results, the covariate “follow-up times” might not be the source
of the heterogeneity because that different follow-up times of included studies could hardly explain the
residual variation due to between-study variance [29]. On the contrary, the differences of mean age of
participants and the duration of treatments could explain part of the between-study variance, meaning
that the two covariates might be part of the sources of the heterogeneity and would affect the effects of
therapies. What’s more, the meta-regression of the mean age of participants had a significant statistical
difference, showing that the effect of multi-modal therapies might decrease with age. This result might
be related to the mental health and capacity of recovery of older adults [47,48]. Besides, the result of
the meta-regression of the duration of treatments tended to be statistically significant. It indicated that
there might be no additional benefit from increasing the duration of therapy for kinesiophobia. Finally,
the goodness of fit of the model used in the meta-regression for these covariates was low, indicating
that the results should be interpreted carefully.
A considerable heterogeneity within the included studies could be seen in the heterogeneity test
in the meta-analysis and the subgroup analysis. The heterogeneity might come from the different
designs of these studies. For example, the included studies had differences in the FITT characteristics
(frequency, intensity, time, environments, and types) of the training plan [49,50]. Moreover, the different
populations of the participants, the different blinding method, and some other factors, especially the
different validities and reliability of the Tampa Scale of Kinesiophobia for participants with different
educational backgrounds, culture, personalities, and types of musculoskeletal disorders [26,27,51],
might lead a heterogeneity within studies.
This review had some limitations. Firstly, few studies reported the detailed pain duration of the
participants or discussed the different effects between gender, leading it infeasible to make subgroup
analysis or meta-regression for these covariates. Secondly, the statistical part of some studies did not
consider the test-retest reliability of the Tampa Scale of Kinesiophobia, setting the test-retest reliability
as 1.00 in their analysis of variance, which was impossible in a subjective questionnaire, so that the
accuracy of their results was affected. Thirdly, in the search strategy, there might be an absence of
data because the scores of the Tampa Scale of Kinesiophobia are usually reported as the secondary
outcome. Finally, some studies didn’t use the Tampa Scale of Kinesiophobia to measure the fear of
physical movements.
The risk of bias was supposed to exist, and the source is various. For example, there were many
musculoskeletal disorders that could lead to a fear of physical movements. Still, not all studies in the
field of physical rehabilitation reported the score of the Tampa Scale of Kinesiophobia. In fact, to all
kinds of musculoskeletal disorders with the following pain, the fear of physical movements was very
common [1]. What’s more, different shortened versions of the Tampa Scale of Kinesiophobia, such as
Int. J. Environ. Res. Public Health 2020, 17, 9439 19 of 22

TSK-13 and TSK-11, were used in other studies [52,53], making these studies could not be included in
the review. Lastly, other resources of publication bias could not be excluded [54–57].
The statistical power of all pooled effect analysis in this review was larger than that in any single
primary study, subgroup analysis, and the heterogeneity test. This result accords with the statistical
law of meta-analysis [29].

5. Conclusions
It could be concluded that (1) Although a large heterogeneity within the included studies existed,
the multi-modal therapies had advantages over uni-modal therapies for kinesiophobia caused by
musculoskeletal disorders with a medium effect size; (2) Multi-modal therapies were more used in
the treatments for chronic pain in the people’s trunk, especially in the neck and low back, and had
an advantage over therapies from a physical perspective no matter the physical therapy was passive
or active; (3) The effect of multi-modal therapies had a decreasing trend with the increase of age;
(4) The influence of different durations of treatments seemed unclear; (5) The effects of multi-modal
therapies might clinically tangible and lasted for a long time; (6) This review’s statistical methods,
which considered the test-retest reliability when combing psychological measurements data that
usually output as a secondary outcome, were mathematically feasible.
Further researchers should pay more attention to rehabilitation from psychophysiology
perspectives when dealing with musculoskeletal disorders. It was suggested to take the fear of
physical movements as one of the main treatment targets and regard the improvement of pain-related
indicators as one of the primary assessment criteria of treatment effectiveness. It might be necessary to
provide standards and official guides of therapies for fear of pain following musculoskeletal disorders.
For example, therapists could benefit from more data on the reliability and validity of the Tampa Scale
of Kinesiphobia for different types of musculoskeletal disorders.

Supplementary Materials: The following are available online at http://www.mdpi.com/1660-4601/17/24/9439/s1,

Figure S1: The result of the GRADE assessment of evidence quality.
Author Contributions: Y.X., D.S. and Y.G., conceived the presented idea, developed the framework, and wrote
the manuscript. G.F. and Y.S., provided critical feedback and contributed to the final version. All authors have
read and agreed to the published version of the manuscript.
Funding: This study was sponsored by the Major Program of the National Social Science Foundation of China
(Grant No. 19ZDA352), National Key R&D Program of China (2018YFF0300903) and K. C. Wong Magna Fund in
Ningbo University.
Conflicts of Interest: The authors declare no conflict of interest.

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