See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/350953797

The short-term impact of combining pain neuroscience education with

exercise for chronic musculoskeletal pain: a systematic review and meta-
analysis

Article  in  Pain · April 2021

DOI: 10.1097/j.pain.0000000000002308

CITATIONS READS

6 981

6 authors, including:

Adrian Ram Matthew David Jones

UNSW Sydney UNSW Sydney
7 PUBLICATIONS   43 CITATIONS    44 PUBLICATIONS   300 CITATIONS   

SEE PROFILE SEE PROFILE

John Booth Diana Perriman

UNSW Sydney Australian National University
31 PUBLICATIONS   1,193 CITATIONS    59 PUBLICATIONS   428 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

3D to 2D Image Registration View project

Patient reported Outcomes after FAI surgery View project

All content following this page was uploaded by Simon J Summers on 03 August 2021.

The user has requested enhancement of the downloaded file.

 Systematic Review and Meta-Analysis

Short-term impact of combining pain neuroscience

education with exercise for chronic
musculoskeletal pain: a systematic review
and meta-analysis
Benjamin Siddalla, Adrian Ramb, Matthew D. Jonesb,c, John Boothb, Diana Perrimana,d,e, Simon J. Summersf,g,h,*

Abstract
Exercise and pain neuroscience education (PNE) have both been used as standalone treatments for chronic musculoskeletal pain. The
evidence supporting PNE as an adjunct to exercise therapy is growing but remains unclear. The aim of this systematic review and meta-
analysis was to evaluate the effect of combining PNE and exercise for patients with chronic musculoskeletal pain, when compared with
exercise alone. A systematic search of electronic databases was conducted from inception to November 6, 2020. A quality effects model
was used to meta-analyze outcomes where possible. Five high-quality randomized controlled studies (n 5 460) were included in this
review. The PEDro scale was used to assess the quality of individual studies, and Grading of Recommendations, Assessment,
Development, and Evaluation analysis was conducted to determine the quality of evidence for each outcome. Meta-analyses were
performed for pain intensity, disability, kinesiophobia, and pain catastrophizing using data reported between 0 and 12 weeks
postintervention. Long-term outcomes (.12 weeks) were only available for 2 studies and therefore were not suitable for meta-analysis.
Meta-analysis revealed a significant difference in pain (weighted mean differences, 22.09/10; 95% confidence interval [CI], 23.38 to
20.80; low certainty), disability (standardized mean difference, 20.68; 95% CI, 21.17 to 20.20; low certainty), kinesiophobia
(standardized mean difference, 21.20; CI, 21.84 to 20.57; moderate certainty), and pain catastrophizing (weighted mean differences,
27.72; 95% CI, 212.26 to 23.18; very low certainty) that favoured the combination of PNE and exercise. These findings suggest that
combining PNE and exercise in the management of chronic musculoskeletal pain results in greater short-term improvements in pain,
disability, kinesiophobia, and pain catastrophizing relative to exercise alone.
Keywords: Chronic musculoskeletal pain, Pain neuroscience education, Exercise therapy, Pain education

1. Introduction overprescription of opiates and other pain modifying drugs for

Chronic musculoskeletal pain has a significant burden on the
healthcare system.17 Currently, there is a crisis related to
Sponsorships or competing interests that may be relevant to content are disclosed
at the end of this article.
D. Perriman and S.J. Summers contributed equally to this manuscript.
a
ANU Medical School, Australian National University, Canberra, Australian Capital
Territory, Australia, b School of Medical Sciences, Faculty of Medicine, University of
New South Wales, Sydney, Australia, c Centre for Pain IMPACT, Neuroscience
Research Australia, Sydney, Australia, d Trauma and Orthopaedic Research Unit,
Canberra Hospital, Canberra, Australian Capital Territory, Australia, e Discipline of
Physiotherapy, Faculty of Health, University of Canberra, Canberra, Australian
Capital Territory, Australia, f Brain Stimulation and Rehabilitation (BrainStAR) Lab,
Western Sydney University, New South Wales, Australia, g Discipline of Sport and
Exercise, Faculty of Health, University of Canberra, Australian Capital Territory,
Australia, h Research School of Biology, Australian National University, Australian
Capital Territory, Australia
*Corresponding author. Address: Discipline of Sport and Exercise, Faculty of Health,
University of Canberra, University Drive, Building 12, Bruce, Australian Capital
Territory 2617, Australia. Tel.: 1 61 409099248. E-mail address: summers.simonj@
gmail.com (S.J. Summers).
Supplemental digital content is available for this article. Direct URL citations appear
in the printed text and are provided in the HTML and PDF versions of this article on
the journal’s Web site (www.painjournalonline.com).
PAIN 00 (2021) 1–11
© 2021 International Association for the Study of Pain
http://dx.doi.org/10.1097/j.pain.0000000000002308
chronic pain with little evidence of long-term effectiveness.6
Exercise therapy is considered the cornerstone treatment for
chronic musculoskeletal pain and is recommended in clinical
guidelines internationally.9,19,37,39 However, reduced adherence
to exercise through fear-avoidance often impacts outcomes.38,41
Pain neuroscience education (PNE) has been shown to reduce
indicators of fear-avoidance behaviour and has, therefore, been
suggested to provide benefits when combined with exercise.29
The evidence supporting PNE adjunct to exercise therapy for
chronic musculoskeletal pain is growing but remains unclear.46
Chronic musculoskeletal pain is pain that persists for longer
than 3 months and perceived to arise from structures such as
bones, joints, and muscles.34 Between 13.5%–47% of people
across the globe live with chronic musculoskeletal pain, the most
common being back and neck pain, as well as painful arthritis (eg,
osteoarthritis).7 Alarmingly, these conditions are the main
contributor to disability globally, with recent reports from the
2019 Global Burden of Disease Study indicating that low back
pain has remained the leading cause of disability since 1990.3,10
These findings highlight that chronic musculoskeletal pain
conditions represent a current and growing, major global health
burden.
There is strong evidence supporting exercise therapy as a
nonpharmacological treatment for chronic pain aimed at re-
ducing pain and disability and improving sleep and overall mood.1
A review of reviews concluded that exercise improves pain

Month 2021
· Volume 00
· Number 00 www.painjournalonline.com 1

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 2
·
B. Siddall et al. 00 (2021) 1–11
severity, disability, and quality of life in patients with chronic pain
and poses little risk of adverse events.15 However, a major barrier
to exercise in patients with chronic pain is fear-avoidance
behaviours, particularly fear of movement (kinesiophobia).20 High
levels of kinesiophobia are associated with reduced exercise
adherence and increased pain and disability in patients with
chronic pain.23,44 It has been demonstrated that patients with low
knowledge of pain neurophysiology display high kinesiophobia.13
This has led to the development of novel education-based
interventions that target patient perceptions of pain to reduce
fear-avoidance behaviours. One such intervention is PNE.29 This
intervention aims to reconceptualize a patient’s understanding of
the biological processes underpinning their pain.29 Pain neuro-
science education has been shown to improve maladaptive
perceptions of pain as well as to produce clinically relevant
decreases in pain catastrophizing and fear avoidance behaviours
across several chronic pain conditions (eg, low back pain and
knee osteoarthritis).32,45 However, clinical improvements in
chronic pain are typically observed in studies that have
implemented PNE with other physical interventions (eg, manual
therapy, trigger point dry-needling, and exercise),22 suggesting
that PNE may be more effective adjunct to therapy with the
potential of amplifying the benefit of exercise.30
There have been several studies evaluating the effect of PNE
when combined with exercise compared with exercise alone for
chronic pain.2,14,25,27,35 However, there has been no synthesis of
this literature, with most systematic reviews focusing on the
effects of pain education and physical interventions more
broadly.22,26,46 A recent systematic review investigated the
combined effect of pain education strategies (eg, pain coping
skills, cognitive behavioural therapy, and PNE) and physical
therapies (eg, manual therapy and exercise) on pain and disability
in chronic pain populations.26 Although an overall pooled
estimate was provided for pain and disability, all types of pain
education and physical therapies were included. Such pooling
limits the ability to provide specific estimates of the effect of PNE
plus exercise vs exercise alone. Understanding this distinction is
particularly important, as exercise therapy is used widely and
almost exclusively in clinical practice above other physical
therapies, such as manual therapy.40 Furthermore, recent
national and international clinical guidelines for chronic pain
support the use of both exercise and pain education as first-line
care,19,37 highlighting the importance of understanding the
combined effects of these interventions. Therefore, the aim of
this review was to synthesize and critically evaluate the effect of
PNE when combined with exercise therapy in chronic musculo-
skeletal pain populations.
2. Methods
This systematic review was registered on PROSPERO
(CRD42020141814), and the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses guidelines were used
throughout the systematic review process.28
2.1. Eligibility criteria
Studies were included if they were randomized controlled trials
(RCTs) of adults ($18 years of age) with chronic musculoskeletal
pain, defined as pain perceived at bones, joints, or muscles that
persisted for longer than 12 weeks. Studies were included if they
compared the combination of PNE and exercise therapy to
exercise therapy alone. Pain neuroscience education was
defined as information delivered to the patient that specifically
Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
PAIN®
explained the neurophysiology of nociception and pain as well as
maladaptive pain perceptions.4 Exercise therapy was defined as
any regimen of physical activities designed with a specific
therapeutic goal (eg, strength, aerobic, and flexibility training).5
Studies where the education method only focused on psycho-
logical or physical aspects of chronic pain were excluded (eg,
cognitive behavioural therapy (CBT), back school programs, and
pain-coping skills training). Included studies were required to
report a pain and/or disability outcome using a validated scale
(eg, visual analogue scale and numerical rating scale) or disease-
specific questionnaire (eg, Oswestry Disability Index and Roland–
Morris Disability Questionnaire).
2.2. Search strategy
Searches were limited to human studies but were not restricted to
English language articles. The following electronic databases
were searched from inception until November 2020: PubMed,
MEDLINE (Ovid), CINAHL, and the Cochrane Central Register of
Controlled Trials (CENTRAL). The specific search strategy used
for these databases is presented in Supplement 1 (available at
http://links.lww.com/PAIN/B363). The clinical trials registries of
the World Health Organization (who.int/ictrp/en), US (Clinical-
Trials.gov), United Kingdom (ukctg.nihr.ac.uk), and Australia/
New Zealand (anzctr.org.au) were also searched. A gray literature
search was undertaken in Google Scholar and the ProQuest
Dissertations & Theses database using general terms (PNE,
chronic musculoskeletal pain, education, and physical activity/
exercise). Finally, reference lists from relevant articles were hand
searched.
2.3. Procedures
The results of the electronic database literature search were
uploaded into Covidence systematic review management soft-
ware (Veritas Health Innovation Ltd, VIC, Australia). After the
removal of duplicates, 2 review authors (B.S. and A.R.)
independently screened the titles and abstracts of studies
obtained through the searches. The 2 authors then independently
assessed the extracted full-text articles for adherence to the
selection criteria. Discrepancies were resolved by consensus of
the project team. This selection process was piloted by the 2
reviewers before commencement of the study screening
process.
The quality of each study was assessed using the Physiotherapy
Evidence Database (PEDro) scale (www.pedro.org.au). The scale
uses 10 of 11 criteria of a quality assessment checklist to assess the
methodological quality and internal validity of studies.24 PEDro
scores were attained by searching for the articles on the PEDro
database. A study with a score of $6 was considered moderate to
high quality, and a score of #4 was considered moderate to low
quality (PEDro, 2020). Two authors independently assessed the
quality of studies that were not published on the PEDro database.
The quality of the study was calculated independently by each
reviewer, and discrepancies were resolved using a third reviewer if
consensus could not be reached.
Assessment of the certainty of evidence was undertaken for
each outcome using the Grading of Recommendations, Assess-
ment, Development, and Evaluation approach.16 Grading of
Recommendations, Assessment, Development, and Evaluation
pro Guideline Development Tool (Evidence Prime, Inc.) was used
to create a summary of findings table. Outcomes were down-
graded if the included studies had a high risk of bias, considerable
heterogeneity of results, did not meet the population,
 Month 2021
· Volume 00
· Number 00
intervention, comparison and outcome (PICO) criteria, the sample
size was low, or if confidence intervals (CIs) crossed the minimal
clinically important difference (MCID). Publication bias was
planned to be assessed using visual inspection of funnel plots;
however, this was not performed because of limited number of
studies included in the review.18
2.4. Data extraction
The primary outcomes for this review were change in pain
intensity and disability between the intervention and comparison
groups measured using a validated scale or disease-specific
questionnaire. Secondary outcomes included differences in
adverse events, self-efficacy, pain catastrophizing, and kinesi-
ophobia. Data were extracted for all available time points after
PNE and exercise interventions. Short-term time points were
defined as #12 weeks, and long-term time points were defined
as .12 weeks.
Two reviewers independently extracted data from the final list
of included studies into a standardized data extraction form. Data
extracted included baseline participant characteristics and
methodological details such as sample size, randomization
methods, and outcome measures. Data characterizing the type
of exercise and PNE provided to participants were also extracted.
This included frequency, duration, adherence, and method of
delivery of exercise and PNE in each study. In the cases where
identified studies did not report data in sufficient detail for the
calculation of an effect size, the study authors were contacted by
email to request the data. If no response was received within 2
Figure 1. PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
www.painjournalonline.com 3
weeks, the study authors were emailed again to request the data.
If no response was received, means and variances were
estimated from the study’s figures using visual data extraction
software.
2.5. Data analysis
To aggregate the data, both weighted mean differences (WMDs)
and standardized effect sizes were used. Weighted mean
differences were used where the data could be expressed as
mean differences between the groups with 95% CIs in the same
units for all studies. Standardized effect sizes (Hedges’ g
standardized mean difference [SMD]) were used where the units
of measurement differed between studies and was calculated
using Effect Size Calculator.8 Meta-analyses were undertaken
using a quality effects model in MetaXL (Epigear International,
Sunrise Beach, Australia; www.epigear.com). A quality effects
model weighs individual studies in a meta-analysis using the
quality score of each study.11 In this way, all available studies can
be included, but their contribution to the overall effect is
dependent on quality. The PEDro score was used in this review
as the indicator of study quality. The significance of the models
was assessed statistically and clinically. Statistical significance
was assessed using the CIs of overall effect sizes of WMDs, such
that if the CI crossed 0 the result was deemed not statistically
significant. Clinical significance was assessed by comparing the
results of these meta-analyzes with the MCID for each outcome
as published in the literature.12,31 A comparison of results with the
MCID was conducted for outcomes where WMD could be
 4
·
B. Siddall et al. 00 (2021) 1–11 PAIN®

calculated. Heterogeneity between the studies was expressed as
an I2 index, which describes the extent of heterogeneity in a meta-
analysis. The degree of heterogeneity as determined by the I2
index was reported as a percentage, such that: 0% to 40% 5 low,
30% to 60% 5 moderate, 50% to 90% 5 substantial, and $75%
5 considerable heterogeneity.18
3. Results
3.1. Study selection
Figure 1 depicts the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses flow diagram. The search identified
261 articles, and 2 articles were identified through the gray
literature search. One hundred seventy-seven articles remained
after deduplication. These underwent title/abstract screening
resulting in the exclusion of 170 studies. The 7 remaining articles
underwent full-text review after which 2 were excluded. Five
articles were retained for qualitative synthesis and meta-analysis.
3.2. Study characteristics and results
All included studies compared outcomes between PNE com-
bined with an exercise program with an exercise program alone.
All studies included patients with chronic musculoskeletal pain.
Of the 5 studies, 2 included a sample of chronic low back pain, 2
with nonspecific chronic spinal pain, and 1 with chronic neck
pain. In all, the 5 studies included 460 participants, with individual
studies including between 52 and 170 participants (Table 1).
Details of the interventions used in each study are described in
Table 2. Interventions varied between studies primarily because of
differences in exercise therapy. The duration of exercise interventions
ranged from 4 to 12 weeks, and the frequency of sessions varied
between once per week to daily. Three studies used the same
exercise program without PNE as a comparison group,2,27,35 and 2
studies used exercise as a comparison,14,25 but these exercises
differed to the intervention group (Table 1). In these 2 studies, exercise
was prescribed as part of usual care, but without the inclusion of PNE
(Table 1). Comparing the effects of different exercises between

Table 1
Study characteristics.
Author (y) Randomisation Total Type of chronic Participant Participant Duration Comparison Intervention Outcome
method sample pain state age mean (SD) sex (M:F) of group group (measure)
size (specific pain Control PNE Control PNE symptoms
subtypes)
Matias Simple 52 Chronic idiopathic 21.3 20.7 6:21 3: .3 mo Neck muscle Neck muscle Pain intensity
et al. randomisation neck pain (2.1) (1.9) 22 endurance and endurance and (VAS), neck
(2019)27 strength exercise strength exercise disability (NDI),
program alone program and PNE kinesiophobia
(TSK-13), and pain
catastrophising
(PCS)
Pires Balanced block 62 Chronic low back 51.0 50.9 12:20 10: .3 mo Aquatic exercise Aquatic exercise Pain intensity
et al. randomisation pain (6.3) (6.2) 20 alone and PNE (VAS), functional
(2015)35 disability (QBPDS),
and kinesiophobia
(TSK-13)
Galan- Simple 170 Nonspecific 49.1 53.0 10:71 24: 93.5 mo Usual Therapeutic Pain intensity
Martin randomisation chronic spinal pain (12.1) (10.7) 65 physiotherapy exercise and PNE (VAS), disability
et al. treatment* (RMDQ),
(2020)14 kinesiophobia
(TSK-11), and pain
catastrophising
(PCS)
Malfliet Block 120 Nonspecific 40.5 39.9 25:35 22: 112.5 mo Mobility, muscle Cognition-targeted Pain (NRS),
et al. randomisation chronic spinal pain (12.9) (12.0) 38 strength, muscle motor control disability (PDI),
(2018)25 (chronic low back endurance, and training and PNE kinesiophobia
pain, failed back general fitness (TSK-17), and pain
surgery syndrome exercises catastrophising
.3 y prior, chronic (PCS)
whiplash, chronic
nontraumatic neck
pain)
Bodes Block 56 Chronic low back 49.2 44.9 6:22 6: $6 mo Multimodal Multimodal Pain intensity
Pardo randomisation pain (10.5) (9.6) 22 exercise program exercise program (NPRS), disability
et al. alone and PNE (RMDQ),
(2018)2 kinesiophobia
(TSK-11), and pain
catastrophising
(PCS)
* Details of the specific exercises were not provided, although authors stated that the exercises were prescribed in accordance with Spanish Society of Physical Medicine and Rehabilitation guidelines.
F, female; M, male; NDI, Neck Disability Index; NPRS, Numeric Pain Rating Scale; NRS, Numeric Rating Scale; PCS, Pain Catastrophising Scale; PDI, Pain Disability Index; PNE, pain neuroscience education; QBPDS, Quebec
Back Pain Disability Scale; RMDQ, Roland–Morris Disability Questionnaire; TSK, Tampa Scale of Kinesiophobia.

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 Month 2021
· Volume 00
· Number 00 www.painjournalonline.com 5

groups was not considered a major problem given that current
evidence suggest that not one type of exercise is more effective than
another for chronic pain.15 All exercise interventions had a therapeutic
intention but varied in content. The types of exercise used were
aquatic exercise, muscle endurance and strength exercises, motor
control exercises, and aerobic exercise. The delivery of the exercise
also differed between studies with either group sessions, one-on-one
sessions, or home-based sessions being applied.
Across the 5 studies, the PNE interventions were consistent for
the content delivered, with each study using Explain Pain as a key
reference.4 However, variation did exist in how PNE was delivered
between studies, relating to the number of sessions participants
received, the duration of these sessions and the timing relative to
the exercise aspect of the intervention. The duration of PNE
sessions ranged from 5 to 120 minutes, and across the studies
PNE was delivered before exercise, concurrently with exercise
sessions and up to a month after cessation of the exercise
sessions (Table 2).
All studies reported pain intensity, disability, and kinesiophobia
as outcomes, and 4 of the 5 studies also included pain
catastrophizing. The mean values for each outcome at reported
timepoints are summarised in Table 3.
3.3. Quality assessment and risk of bias
The quality assessment for each study as determined with PEDro
is outlined in Table 4. All 5 included studies were RCTs of
moderate to high quality ($6 PEDro score). The most common

Table 2
Intervention characteristics.
Author, y Exercise details PNE details Adverse
Type of Frequency Session Program Method of Type Frequency Session Method of events
exercise duration length delivery duration delivery
Matias Exercises Weekly (in wk Increasing 4 wk Supervised PNE based on Weekly Decreasing Group sessions NR
et al. aimed at 2-4 of inverse to time group sessions Explain Pain from 30 min in with 2-5
(2019) increasing the intervention) spent doing with 2-5 and Louw et al. session 1 to 5 participants;
27
endurance and PNE (maximum participants (2013) minutes in booklet
strength of the 25 min) session 4 included
deep neck
flexors and
extensors and
scapular
stabiliser
muscles
Pires Aquatic Biweekly 30-50 min 6 wk Supervised PNE based on Two sessions 90 min Group sessions 0
et al. exercise group sessions Explain Pain immediately
(2015) with 6-9 and Nijs et al. before exercise
35
participants (2011) intervention
Galan- Coordination, Triweekly 60 min 6 wk Supervised PNE with Two sessions Initial 4 Group 0
Martin strength, and group sessions reference to per week for 2 sessions: 90 sessions; book
et al. resistance Explain Pain wk before min. included in
(2020) training exercise. One Final 2 penultimate
14
exercises session per sessions: 120 session
including week for 2 wk min.
flexibility and after exercise.
joint mobility
exercises
Malfliet Sensorimotor ;Weekly (15 NR 12 wk One-on-one PNE based on Three sessions NR One group NR
et al. control training sessions sessions Explain Pain session, one
(2018) using a time- overall) home-based
25
contingent online module
approach and and one
graded individual
introduction of session.
feared Concepts were
movements reinforced
during exercise
sessions.
Bodes Multimodal MCE and MCE and 12 wk Home-based PNE based on Two sessions, 30-50 min Group sessions 0
Pardo exercise stretching: stretching: 15 exercises with Explain Pain one before the with 4-6
et al. program Twice daily. min. Aerobic 2 supervised and Pain in exercise participants;
(2018)2 involving MCE, Aerobic exercise: 20- sessions Motion intervention leaflet included
stretching, and exercise: Daily 30 min and one a mo
aerobic after
exercise
MCE, motor control exercise; NR, not reported; PNE, pain neuroscience education.

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 6
·
B. Siddall et al. 00 (2021) 1–11 PAIN®

reasons for a reduction in score was a failure to blind subjects and
therapists as well as not completing an intention-to-treat analysis.
The PEDro score for 4 studies was taken from the PEDro
database,2,14,25,35 and one study required calculation of the
PEDro score by the authors.27
3.4. Synthesis of results
Short-term outcomes (#12 weeks) were available for all 5 studies.
Long-term outcomes (.12 weeks) were only available for 2 studies
and, therefore, were not suitable for meta-analysis. All 5 studies were
included in a meta-analysis of the short-term effect (#12 weeks) of
PNE and exercise intervention on pain, disability, and kinesiophobia
outcomes. Four studies were included in a meta-analysis of the short-
term effect on pain catastrophizing. Subgroup analyses based on the
type of exercise and anatomical site of pain were not conducted as
per the planned protocol because of limited number of studies.
3.5. Pain intensity
Pain outcomes were reported in all studies, and it was observed that
PNE combined with exercise significantly reduced short-term pain
intensity scores compared with exercise alone, but high levels of
heterogeneity were detected (WMD, 22.09; 95% CI, 23.38 to
20.80; I2 5 86%). The mean estimate for difference in pain score lies
within the published interquartile range for MCID for chronic pain
[1.2-3.9], and the mean estimate of 2.09 is very close to the median
estimate of 2.3.33 See Figure 2.

Table 3
Results.
Author, y Comparison PNE group Outcomes Comparison group mean (SD) PNE and exercise group mean (SD)
group sample sample size Baseline 0 wk 4 wk 12 6 mo 9 mo Baseline 0 wk 4 wk 12 6 mo 9 mo
size (n) (n) wk wk
Matias et al. 27 25 Pain (VAS) 4.3 (2.9) 3.1 NR 3.6 NR NR 4.0 (2.3) 3.0 NR 3.4 NR NR
(2019)27 (2.3) (2.4) (2.3) (2.3)
Disability (NDI) 21.4 14.7 NR 13.4 NR NR 20.4 15.2 NR 14.1 NR NR
(8.6) (5.2) (7.4) (8.1) (9.5) (8.7)
Kinesiophobia 23.0 23.2 NR 21.8 NR NR 26.3 22.2 NR 19.8 NR NR
(TSK-13) (6.2) (5.1) (7.7) (6.1) (5.1) (7.7)
Pain 20.9 15.1 NR 15.9 NR NR 19.4 13.3 NR 12.7 NR NR
catastrophizing (13.1) (10.7) (11.6) (11.6) (10.1) (10.7)
(PCS)
Pires et al. 32 30 Pain (VAS) 42.4 27.6 NR 35.8 NR NR 43.4 (23) 20.6 NR 18.0 NR NR
(2015)35 (21.2) (17.2) (28) (19) (19)
Disability 28.1 20.4 NR 25.9 NR NR 32.3 (14) 21.2 NR 19.2 NR NR
(QBPDS) (13.6) (12.3) (15.7) (15.8) (14.8)
Kinesiophobia 29.1 27.5 NR 26.5 NR NR 28.6 (6) 25.2 NR 23.2 NR NR
(TSK-13) (5.6) (6.2) (7.9) (4.7) (6.3)
Galan-Martin 81 89 Pain (VAS) 67.2 58.4 NR NR 59.7 NR 74.1 26.7 NR NR 27 NR
et al. (2020) (14.3) (17.7) (19.8) (14.5) (18) (16.2)
14
Disability 8 (4.7) 7.6 NR NR 7.7 NR 9.2 (4.8) 3.3 NR NR 3.3 NR
(RMDQ) (4.6) (4.8) (3.5) (3.8)
Kinesiophobia 27.5 26.1 NR NR 26.3 NR 28.9 17.1 NR NR 17.2 NR
(TSK-11) (7.1) (6.3) (7.6) (6.6) (4) (4.7)
Pain 27.9 26.6 NR NR 24.2 NR 30.3 15.4 NR NR 15.5 NR
catastrophising (9.1) (9.7) (10.3) (8.7) (7.3) (7.2)
(PCS)
Malfliet et al. 60 60 Pain (NRS) 5 (1.9) 3.3 NR 3.8 NR 3.4 5.2 (1.9) 2.5 NR 3.0 NR 2.7
(2018)25 (2.4) (2.6) (2.4) (2.3) (2.5) (2.4)
Disability (PDI) 21.6 14.5 NR 14.2 NR 13.9 21.8 9.4 NR 7.9 NR 8.1
(14.0) (13.6) (13.3) (12.8) (14.0) (13.3) (13.1) (12.4)
Kinesiophobia 36.7 33 NR 33.7 NR 32.9 34.4 24.4 NR 23.9 NR 24
(TSK-17) (7.0) (5.5) (7.0) (6.3) (7.0) (6.5) (6.8) (6.1)
Pain 16.9 12.5 NR 9.6 NR 9.5 16.5 8.9 NR 6.6 NR 6.1
catastrophising (10.2) (9.6) (9.2) (9.1) (10.2) (9.3) (8.9) (8.8)
(PCS)
Bodes Pardo 28 28 Pain (NPRS) 7.8 (1.2) 7.1 6.0 4.8 NR NR 7.9 (1.4) 5.3 3.9 2.7 NR NR
et al. (2018)2 (1.6) (1.2) (1.9) (1.6) (1.9) (1.9)
Disability 12.6 NR 11.0 9.8 NR NR 12.0 NR 8.5 6.4 NR NR
(RMDQ) (1.4) (1.8) (2.3) (1.6) (2.0) (2.3)
Kinesiophobia 28.1 NR 26.1 24.1 NR NR 28.7 NR 20.1 16.1 NR NR
(TSK-11) (5.7) (5.3) (5.5) (6.5) (4.2) (2.3)
Pain 32.1 NR 28.7 26.9 NR NR 34.1 NR 22.2 18.2 NR NR
catastrophising (5.0) (5.4) (5.4) (7.5) (8.8) (7.2)
(PCS)
n, number; NDI, Neck Disability Index; NPRS; Numerical Pain Rating Scale; NR; not reported; NRS, Numerical Rating Scale; PCS, Pain Catastrophising Scale; PDI, Pain Disability Index; QBPDS, Quebec Back Pain Disability Scale;
RMDQ, Roland–Morris Disability Questionnaire; SD, standard deviation; TSK, Tampa Scale of Kinesiophobia; VAS, visual analogue scale.

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 Month 2021
· Volume 00
· Number 00 www.painjournalonline.com 7

Table 4 estimated MCID of 5.2 for the Pain Catastrophizing Scale;

Quality assessment. however, the lower CI (23.18) did not.31 See Figure 5.
Study Question* Score
1 2 3 4 5 6 7 8 9 10 11 3.9. Quality of evidence
Matias et al. (2019)27 Y Y Y Y N N Y Y N Y Y 7 The Grading of Recommendations, Assessment, Development, and
Pires et al. (2015)35 Y Y Y Y N N Y Y Y Y Y 8 Evaluation certainty of evidence was low for difference in short-term
Galan-Martin et al. (2020)14 Y Y Y Y N N Y Y N Y Y 7
pain intensity and disability, moderate for difference in short-term
25
kinesiophobia, and very low for difference in short-term pain
Malfliet et al. (2018) Y Y N Y Y N Y Y N Y Y 7 catastrophizing. The primary reason for downgrading of evidence
2
Bodes Pardo et al. (2018) Y Y Y Y N N N Y N Y Y 6 was the significant heterogeneity detected in the meta-analysis of
* 1, eligibility criteria were specified (not counted in PEDro score); 2, subjects were randomly allocated to each outcome. Further explanations for downgrading of evidence can
groups; 3, allocation was concealed; 4, the groups were similar at baseline regarding the most important be found in Table 5.
prognostic indicators; 5, there was blinding of all subjects; 6, there was blinding of all therapists who
administered the therapy; 7, there was blinding of all assessors who measured at least one key outcome; 8,
measures of at least one key outcome were obtained from more than 85% of the subjects initially allocated to
groups; 9, all subjects for whom outcome measures were available received the treatment or control 4. Discussion
condition as allocated or, where this was not the case, data for at least one key outcome were analysed by
“intention to treat”; 10, the results of between-group statistical comparisons are reported for at least one key This systematic review sought to establish whether PNE
outcome; and 11, the study provides both point measures and measures of variability for at least one key combined with exercise is more efficacious in the management
outcome.
N, no; Y, yes.
of chronic musculoskeletal pain than exercise alone. Five RCTs (n
5 460) included for meta-analysis reported data for differences in
short-term (#12 weeks) pain intensity, disability, and kinesio-
3.6. Disability phobia, and 4 of the 5 studies (n 5 398) reported data for
Disability outcomes were reported in all studies, and it was observed differences in pain catastrophizing. Meta-analyses demonstrated
that PNE combined with exercise produced a statistically significant significant differences for all outcomes favouring the combination
medium effect on short-term disability compared to exercise alone, but of PNE and exercise when compared with exercise alone.
considerable heterogeneity was detected in the analysis (SMD, 20.68; Notably, the difference in pain intensity lay within the published
95% CI, 21.17 to 20.20; I2 5 81%). See Figure 3. interquartile range for MCID for chronic pain, and with the
exception of the lowest CI, the difference in pain catastrophising
surpassed the MCID. These novel findings suggest that patient
3.7. Kinesiophobia outcomes are improved to a greater extent when exercise is
All studies reported kinesiophobia scores using different versions delivered with PNE, rather than alone, for patients with chronic
of the Tampa Scale of Kinesiophobia. Analysis revealed a musculoskeletal pain. These findings should be interpreted with
statistically significant and large effect of PNE combined with caution as heterogeneity between studies was high, and the
exercise on short-term kinesiophobia scores compared with certainty of evidence was very low to moderate.
exercise alone, but considerable heterogeneity was detected Pain neuroscience education combined with exercise resulted
(SMD, 21.20; CI, 21.84 to 20.57; I2 5 88%). See Figure 4. in significant improvements in short-term pain and disability. A
previous review, by Marris et al.,26 reported nonsignificant
improvements in pain and disability in chronic pain patients who
3.8. Pain catastrophizing
received combined pain education and physical therapy com-
Four studies2,14,25,27 reported pain catastrophizing as an out- pared with physical therapy or usual therapy alone. These
come using the Pain Catastrophizing Scale. It was observed that conflicting findings may be related to the fact that the present
PNE combined with exercise significantly reduced pain cata- review included studies that used PNE which focused on pain
strophizing scores compared with exercise alone, but consider- neurophysiology and exercise-based interventions. Whereas,
able heterogeneity was detected (WMD, 27.72; 95% CI, 212.26 Marris et al. (2019) included studies that used a wide range of
to 23.18; I2 5 83%). The mean difference exceeded the education modalities (PNE, back-school programs, therapeutic

Figure 2. Quality effects meta-analysis of difference in short-term pain intensity (/10) of PNE and exercise compared with exercise alone. PNE, pain neuroscience
education.

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 8
·
B. Siddall et al. 00 (2021) 1–11
Figure 3. Quality effects meta-analysis of difference in short-term disability of PNE and exercise compared with exercise alone. PNE, pain neuroscience education.
patient education, and CBT) and physical therapies (exercise,
manual therapy, motor control therapy, and trigger point dry-
needling), resulting in the analysis of a more heterogenous group
of studies. Thus, the present review extends existing work by
synthesising the combined effect of PNE and exercise therapy,
demonstrating positive outcomes for pain and disability in
patients with chronic musculoskeletal pain.
The short-term improvements in pain intensity with combined
PNE and exercise (22.09/10) lay within the published interquartile
range for MCID of chronic pain (1.2-3.9).33 Although this finding
supports clinically meaningful effects on pain, one study by
Matias et al. (2019) reported a difference of just 20.2/10 which
was lower than all other included studies. The Matias et al. (2019)
study implemented relatively fewer hours of exercise (;1 hour
compared with 8-64 hours), which may explain this difference.
The combination of exercise and PNE has been recommended
for the treatment of pain,29 and our results suggest that a
minimum amount of exercise may be needed to enable the
benefit of PNE; however, there were insufficient studies to
interrogate this hypothesis. In addition, Galan-Martin et al. (2020)
reported much greater decreases in pain compared with the
other included RCTs. Participants in this study spent a sub-
stantially greater amount of time learning PNE (10 hours)
compared with the other studies (1-3 hours). This suggests that
greater knowledge of pain neurophysiology may result in more
favourable outcomes. Although plausible, only one of the
included studies reported changes in knowledge of pain, and
for this reason, it was not possible to assess this relationship.
The reduction in short-term disability observed (SMD, 20.68)
was consistent with that reported in the previous review by Marris
Figure 4. Quality effects meta-analysis of difference in kinesiophobia of PNE and exercise compared with exercise alone. PNE, pain neuroscience education.
Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
PAIN®
et al. (2019) (SMD, 20.79). One of the key target concepts of PNE
is that “pain is an unreliable indicator of the presence or extent of
tissue damage.”29 Reconceptualizing pain in this way and having
patients engage with exercise at the same time may help re-
enforce that patients are safe to move, reducing their perceived
levels of disability. This suggestion is supported by the fact that all
studies demonstrating a significant effect on disability2,14,25 also
displayed significant reductions in kinesiophobia, whereas those
that showed no effect on disability27,35 demonstrated no
difference in kinesiophobia. In addition, the participants from
Bodes Pardo et al. (2018) and Galan-Martin et al. (2020) that
showed the biggest effect on disability, compared with partici-
pants in the other included RCTs, exercised more frequently ($3
sessions per week vs 1-2 sessions per week) and exercised
longer each session (60 minutes vs 10-50 minutes), suggesting
that dose of exercise may also influence this relationship.
Understanding how disability is influenced by dose of exercise
and accumulative exposure to PNE is an important consideration
for future research.
Short-term improvements were found in kinesiophobia and
pain catastrophizing after PNE and exercise. Previous reviews
have reported improvements in kinesiophobia and pain
catastrophizing in chronic musculoskeletal pain populations
that received PNE only compared with those that did not.22,45
However, in these studies improvements did not result in
concomitant improvements in pain and disability between PNE
and non-PNE groups. Our review is the first to demonstrate
that the combination of PNE and exercise favors decreased
kinesiophobia (SMD, 21.20) and pain catastrophizing (WMD,
27.72) as well as improvements in pain and disability above
 Month 2021
· Volume 00
· Number 00 www.painjournalonline.com 9

Figure 5. Quality effects meta-analysis of difference in pain catastrophizing (/52) of PNE and exercise compared with exercise alone. PNE, pain neuroscience
education.

exercise alone. These findings together with previous research
suggest that combining PNE with exercise may be more
effective on patient outcomes than exercise or PNE alone. The
positive effects of PNE and exercise may be related to the
mediation of kinesiophobia and pain catastrophizing. Media-
tion is an indirect effect of an intervention whereby changes in
one outcome lead to changes in another.43 It is possible that as
an adjunct PNE reduces participants’ fear and anxiety relating
to movement, producing analgesia by reducing the affective-
emotional aspect of pain and improving engagement with
exercise.29 This effect combined with mechanisms of
exercise-induced hypoalgesia36 may explain why greater
outcomes are observed when these interventions are
combined.
The results of this review should be viewed in light of
methodological limitations. There were a small number of
included studies. This was due to the strict inclusion criteria
regarding suitable PNE and exercise interventions. In addition,
high levels of heterogeneity were detected in the analyses of all
outcomes, and wide CIs were observed. This is likely due to
variations in the length of interventions of the included studies as
well as variability in the frequency and duration of both the
exercise and PNE sessions. In addition, studies that used a
different exercise as part of usual care, as opposed to the same
exercise type without PNE, may also have contributed to this
heterogeneity and wide CIs. With 5 studies, it was not possible to
perform further subgroup analyses, which may have helped
determine possible sources of the heterogeneity observed in the

Table 5
Summary of findings.
Outcomes Anticipated absolute effects* (95% CI)Relative effect № of Certainty of the Comments
Risk with Risk with PNE combined (95% CI) participants evidence (GRADE)
exercise alone with exercise (studies)
Difference in short-term — MD 2.09 lower (3.36 lower — 460 (5 RCTs) A lower score indicates a
pain intensity scale from: to 0.8 lower) LOW†‡ decrease in pain. A change
0 to 10 greater than 1 is considered a
clinically important difference.1
Difference in short-term — SMD 0.68 lower (1.17 — 460 (5 RCTs) A negative effect size indicates
disability lower to 0.2 lower) LOW†§ a reduction in disability
Difference in short-term — SMD 1.2 lower (1.84 lower — 460 (5 RCTs) A negative effect size indicates
kinesiophobia to 0.57 lower) MODERATE† a decrease in kinesiophobia
Difference in pain — MD 7.72 lower (12.26 — 398 (4 RCTs) A lower score indicates a
catastrophising assessed lower to 3.18 lower) VERY LOW†‡║ decrease in pain
with: Pain Catastrophising catastrophising. A change of
Scale from: 0 to 52 more than 5.2 indicates a
clinically important difference.2
PNE combined with exercise compared with exercise alone for managing chronic musculoskeletal pain. Patient or population: adults with chronic musculoskeletal pain setting: Intervention: PNE combined with exercise
comparison: exercise alone.
GRADE working group grades of evidence.
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.
* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Explanations:
† Considerable heterogeneity detected in results (I2 above 75%).
‡ Lower CI is not considered a clinically important difference.
§ Lower CI crosses SMD of 20.5.
║ Sample size below 400.
CI, confidence interval; GRADE, Grading of Recommendations, Assessment, Development, and Evaluation; MD, mean difference; SMD, standardised mean difference.

Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
 10
·
B. Siddall et al. 00 (2021) 1–11
results. Despite these limitations, this review has several
strengths. A prospective protocol was lodged, in accordance
with current recommendations in the field.21 Only RCTs using
PNE were included in the analyses. Previous reviews have pooled
RCTs with different education programs (PNE, CBT, and back-
school) and have not been able to draw conclusions specifically
related to PNE.26 Similarly, only studies that used exercise-based
programs, as opposed to any physical therapy modality (manual
therapy, dry-needling, etc.), were included in this review. This
increases the relevance of our results to exercise-based
programs targeting chronic musculoskeletal pain.
4.1. Implications for future research
This review highlights that PNE combined with exercise may be
more efficacious in improving pain and disability, as well as
kinesiophobia and pain catastrophizing, in individuals with
chronic musculoskeletal pain compared with exercise alone.
Future research should aim to better understand the impact of
PNE dose and exercise dose on improvements in outcomes. This
could be investigated using metaregression.42 Although the
sample size in this review was too small to draw meaningful
conclusions with a metaregression, future reviews applying
metaregression to individual patient data would be valuable to
better understand this relationship.18 An improvement in report-
ing of change in pain neurophysiology knowledge is also
important in elucidating the role PNE plays as an adjunct therapy
to exercise. Only one study in this review measured changes in
pain neurophysiology knowledge, and for this reason, it was not
possible to analyze this outcome. Finally, more RCTs need to
report the long-term effectiveness of combined PNE and exercise
programs for managing chronic musculoskeletal pain.
5. Conclusion
This review found that combining PNE and exercise resulted in
greater improvements in pain, disability, kinesiophobia, and pain
catastrophizing compared with exercise alone. Notably, the
improvements in pain intensity exceeded the MCID. These data
have important clinical implications, suggesting that greater
improvements in patient outcomes may be observed when PNE
is delivered alongside exercise for patients with chronic muscu-
loskeletal pain. However, the findings of this review should be
interpreted with caution as heterogeneity between studies was
high, and the certainty of evidence was very low to moderate.
Conflict of interest statement
The authors have no conflicts of interest to declare.
Acknowledgements
Thanks to Dianne Walton-Sonda (ACT Health Library) and Rachel
Karasick (ANU, Hancock Library) for their help with developing
and running the searches.
Appendix A. Supplemental digital content
Supplemental digital content associated with this article can be
found online at http://links.lww.com/PAIN/B363.
Article history:
Received 6 December 2020
Received in revised form 17 March 2021
Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
PAIN®
Accepted 7 April 2021
Available online 9 April 2021
References
[1] Ambrose KR, Golightly YM. Physical exercise as non-pharmacological
treatment of chronic pain: why and when. Best Pract Res Clin Rheumatol
2015;29:120–30.
[2] Bodes Pardo G, Lluch Girbes E, Roussel NA, Gallego Izquierdo T,
Jimenez Penick V, Pecos Martin D. Pain neurophysiology education and
therapeutic exercise for patients with chronic low back pain: a single-blind
randomized controlled trial. Arch Phys Med Rehabil 2018;99:338–47.
[3] Briggs AM, Woolf AD, Dreinhofer K, Homb N, Hoy DG, Kopansky-Giles D.
Reducing the global burden of musculoskeletal conditions. Bull World
Health Organ 2018;96:366–8.
[4] Butler DS, Moseley GL. Explain Pain: (Revised and Updated. 2nd Ed.
Doctorzed Publishing, Adelaide, Australia 2013.
[5] Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise,
and physical fitness: definitions and distinctions for health-related
research. Public Health Rep 1985;100:126–31.
[6] Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I. The
effectiveness and risks of long-term opioid therapy for chronic pain: a
systematic review for a National Institutes of Health Pathways to
Prevention Workshop. Ann Intern Med 2015;162:276–86.
[7] Cimmino MA, Ferrone C, Cutolo M. Epidemiology of chronic
musculoskeletal pain. Best Pract Res Clin Rheumatol 2011;25:173–83.
[8] Coe R. Effect Size Calculator—CEM. Centre for Evaluation and
Monitoring, 2020. Accessed 19 June 2020. Available at: https://www.
cem.org/effect-size-calculator.
[9] Daenen L, Varkey E, Kellmann M, Nijs J. Exercise, not to exercise, or how
to exercise in patients with chronic pain? Applying science to practice.
Clin J Pain 2015;31:108–14.
[10] Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in
204 countries and territories, 1990-2019: a systematic analysis for the
Global Burden of Disease Study 2019. Lancet 2020;396:1204–22.
[11] Doi SA, Thalib L. A quality-effects model for meta-analysis. Epidemiology
2008;19:94–100.
[12] Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical
importance of changes in chronic pain intensity measured on an 11-point
numerical pain rating scale. PAIN 2001;94:149–58.
[13] Fletcher C, Bradnam L, Barr C. The relationship between knowledge of
pain neurophysiology and fear avoidance in people with chronic pain: a
point in time, observational study. Physiother 2016;32:271–6.
[14] Galan-Martin MA, Montero-Cuadrado F, Lluch-Girbes E, Coca-Lopez
MC, Mayo-Iscar A, Cuesta-Vargas A. Pain neuroscience education and
physical therapeutic exercise for patients with chronic spinal pain in
Spanish physiotherapy primary care: a pragmatic randomized controlled
trial. J Clin Med 2020;9:1201.
[15] Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical
activity and exercise for chronic pain in adults: an overview of Cochrane
Reviews. Cochrane Database Syst Rev 2017;4:CD011279.
[16] Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P.
GRADE: an emerging consensus on rating quality of evidence and
strength of recommendations. Bmj 2008;336:924–6.
[17] Health AIo, Welfare. Chronic pain in Australia. Canberra: AIHW, 2020.
[18] Higgins JPTT J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane
Handbook for Systematic Reviews of Interventions, 2020. Accessed 17
February 2020. Available at: www.training.cochrane.org/handbook.
[19] Hooten MT D, Hora J, Johnson C, Bianco J, Schweim K, Walker N, Clavel
A, Nooman MP, Reznikoff C, Bonte B, Wainio J, Kirksson E, Hansen A,
Dvorkin J, Hadzik S, Institute for Clinical Systems Improvement. Pain:
Assessment, Non-Opioid Treatment Approaches and Opioid
Management Care for Adults, 2017. Accessed 18 November 2020
Available at: https://www.icsi.org/wp-content/uploads/2019/10/Pain-
Interactive-7th-V2-Ed-8.17.pdf.
[20] Larsson C, Ekvall Hansson E, Sundquist K, Jakobsson U. Impact of pain
characteristics and fear-avoidance beliefs on physical activity levels
among older adults with chronic pain: a population-based, longitudinal
study. BMC Geriatr 2016;16:50.
[21] Lee H, Lamb SE, Bagg MK, Toomey E, Cashin AG, Moseley GL.
Reproducible and replicable pain research: a critical review. PAIN 2018;
159:1683–9.
[22] Louw A, Zimney K, Puentedura EJ, Diener I. The efficacy of pain
neuroscience education on musculoskeletal pain: a systematic review of
the literature. Physiother 2016;32:332–55.
[23] Luque-Suarez A, Martinez-Calderon J, Falla D. Role of kinesiophobia on
pain, disability and quality of life in people suffering from chronic
 Month 2021
· Volume 00
· Number 00
musculoskeletal pain: a systematic review. Br J Sports Med 2019;53:
554–9.
[24] Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability
of the PEDro scale for rating quality of randomized controlled trials. Phys
Ther 2003;83:713–21.
[25] Malfliet A, Kregel J, Coppieters I, De Pauw R, Meeus M, Roussel N. Effect
of pain neuroscience education combined with cognition-targeted motor
control training on chronic spinal pain: a randomized clinical trial. JAMA
Neurol 2018;75:808–17.
[26] Marris D, Theophanous K, Cabezon P, Dunlap Z, Donaldson M. The
impact of combining pain education strategies with physical therapy
interventions for patients with chronic pain: a systematic review and
meta-analysis of randomized controlled trials. Physiother Theor Pract
2021;37:461–72.
[27] Matias BA, Vieira I, Pereira A, Duarte M, Silva AG. Pain neuroscience
education plus exercise compared with exercise in university students
with chronic idiopathic neck pain. Int J Ther Rehabil 2019;26:1–14.
[28] Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting
items for systematic reviews and meta-analyses: the PRISMA statement.
PLoS Med 2009;6:e1000097.
[29] Moseley GL, Butler DS. Fifteen years of explaining pain: the past, present,
and future. J Pain 2015;16:807–13.
[30] Moseley L. Combined physiotherapy and education is efficacious for
chronic low back pain. Aust J Physiother 2002;48:297–302.
[31] National Guideline C. National institute for health and care excellence:
clinical guidelines. In: Low Back Pain and Sciatica in Over 16s:
Assessment and Management. London: National Institute for Health
and Care Excellence (UK) Copyright © NICE, 2016.
[32] Nijs J, Paul van Wilgen C, Van Oosterwijck J, van Ittersum M, Meeus M.
How to explain central sensitization to patients with ’unexplained’ chronic
musculoskeletal pain: practice guidelines. Man Ther 2011;16:413–8.
[33] Olsen MF, Bjerre E, Hansen MD, Tendal B, Hilden J, Hróbjartsson A.
Minimum clinically important differences in chronic pain vary considerably
by baseline pain and methodological factors: systematic review of
empirical studies. J Clin Epidemiol 2018;101:87–106.e2.
[34] Perrot S, Cohen M, Barke A, Korwisi B, Rief W, Treede RD. The IASP
classification of chronic pain for ICD-11: chronic secondary
musculoskeletal pain. PAIN 2019;160:77–82.
Copyright © 2021 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
View publication stats
www.painjournalonline.com 11
[35] Pires D, Cruz EB, Caeiro C. Aquatic exercise and pain neurophysiology
education versus aquatic exercise alone for patients with chronic low
back pain: a randomized controlled trial. Clin Rehabil 2015;29:538–47.
[36] Rice D, Nijs J, Kosek E, Wideman T, Hasenbring MI, Koltyn K. Exercise-
induced hypoalgesia in pain-free and chronic pain populations: state of
the art and future directions. J Pain 2019;20:1249–66.
[37] Scottish Intercollegiate Guidelines Network S. Mangement of chronic
pain 2013, 2019. Accessed 18 November 2020. Available at: https://
www.sign.ac.uk/media/1108/sign136_2019.pdf.
[38] Slade SC, Patel S, Underwood M, Keating JL. What are patient beliefs
and perceptions about exercise for nonspecific chronic low back pain? A
systematic review of qualitative studies. Clin J Pain 2014;30:995–1005.
[39] Society NAS. Diagnosis and treatment of low back pain, 2020. Accessed
18 November 2020. Available at: https://www.spine.org/Portals/0/
assets/downloads/ResearchClinicalCare/Guidelines/LowBackPain.pdf.
[40] Summers SJ, Schabrun SM, Chipchase LS. The type and pain provoking
nature of exercise prescribed for low back pain: a survey of Australian
health professionals. Musculoskelet Sci Pract 2018;38:37–45.
[41] Taulaniemi A, Kankaanpaa M, Rinne M, Tokola K, Parkkari J, Suni JH.
Fear-avoidance beliefs are associated with exercise adherence:
secondary analysis of a randomised controlled trial (RCT) among
female healthcare workers with recurrent low back pain. BMC Sports
Sci Med Rehabil 2020;12:28.
[42] Thompson SG, Higgins JPT. How should meta-regression analyses be
undertaken and interpreted? Stat Med 2002;21:1559–73.
[43] VanderWeele T, Vansteelandt S. Mediation analysis with multiple
mediators. Epidemiologic Methods 2014;2:95–115.
[44] Vlaeyen JW, Linton SJ. Fear-avoidance and its consequences in chronic
musculoskeletal pain: a state of the art. PAIN 2000;85:317–32.
[45] Watson JA, Ryan CG, Cooper L, Ellington D, Whittle R, Lavender M. Pain
neuroscience education for adults with chronic musculoskeletal pain: a
mixed-methods systematic review and meta-analysis. J Pain 2019;20:
1140 e1–e22.
[46] Wood L, Hendrick PA. A systematic review and meta-analysis of pain
neuroscience education for chronic low back pain: short-and long-term
outcomes of pain and disability. Eur J Pain 2019;23:234–49.