10 1002@ejp 1666

Accepted Article
Article type : Review Article
Prescription of exercises for the treatment of chronic pain along the continuum of nociplastic
pain: a systematic review with meta-analysis
Running title: Prescription of exercises for chronic pain
Katherinne Ferro Moura Francoa,b*; Dorine Lenoirb,c,d; Yuri Rafael dos Santos Francoa; Felipe
José Jandre Reisd,e; Cristina Maria Nunes Cabrala; Mira Meeusb,d,f.
a Master’s and Doctoral Program in Physical Therapy, Universidade Cidade de São Paulo, São
Paulo, Brazil
b Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health
Sciences, Ghent University, Ghent, Belgium
c Department of Physiotherapy, Human Physiology and Anatomy (KIMA), Faculty of Physical
Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium
d Pain in Motion International Research Group, www.paininmotion.be
e Physical Therapy Department, Instituto Federal do Rio de Janeiro, Rio de Janeiro, Brazil
f MOVANT Research Group, Department of Rehabilitation Sciences and Physiotherapy, Faculty
of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
*Corresponding author: Katherinne Ferro Moura Franco, Rua Cesário Galeno 475, Tatuapé, São
Paulo, SP, Brazil, Zipcode: 03071-000. Telephone number: +551121781214. e-mail:
[email protected]
Category: Review
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/EJP.1666
This article is protected by copyright. All rights reserved
Funding Sources: This study was funded by São Paulo Research Foundation (FAPESP – grant
Accepted Article
number 2018/14109-8). FAPESP was not involved with data collection or analysis.
The authors declare that there was no conflict of interest.
Significance: The pain mechanism must be considered to optimize exercise prescription in

patients with different chronic pain profiles. The main message of this article is that low to
moderate intensity global exercises performed for a long period of treatment should be performed
in patients with nociplastic pain predominance. Additionally, focused and intense exercises for a
short period of treatment can be prescribed for patients with nociceptive pain predominance.

ABSTRACT
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Background and Objective: To compare different exercise prescriptions for patients with chronic
pain along the continuum of nociplastic pain: fibromyalgia, chronic whiplash-associated disorders
(CWAD), and chronic idiopathic neck pain (CINP). Databases and Data Treatment:
Randomized controlled trials comparing different exercise parameters were included. The search
was performed in the databases Cochrane Central Register of Controlled Trials, MEDLINE,
EMBASE, CINAHL, and PEDro. Data on the parameters for the physical exercise programs for
pain management were extracted for analysis. Results: Fifty studies with 3,562 participants were
included. For fibromyalgia, both aerobic or strengthening exercises were similar and better than
stretching exercises alone. Exercises could be performed in 50- to 60-minute supervised sessions,
2 to 3 times a week, for 13 weeks or more. For CWAD, body awareness exercises were similar to
combined exercises, and there was no difference in adding sling exercises to a strengthening
exercise program. The exercises could be performed in 90-minute supervised sessions, twice a
week, for 10 to 16 weeks. For CINP, motor control exercises and nonspecific muscle
strengthening had a similar effect. Exercises could be performed in 30- to 60-minute supervised
sessions, 2 to 3 times a week, for 7 to 12 weeks. Conclusions: The choice of parameters regarding
exercises should emphasize global exercises in nociplastic pain conditions (such as fibromyalgia
and CWAD) and specific exercises in non-nociplastic pain conditions (such as CINP) and be
based on patient's preference and therapist's skills.
Prospero registration number: CRD42019123271
Keywords: Fibromyalgia; Chronic whiplash-associated disorders; Chronic idiopathic neck pain;
Exercise therapy; Central sensitization.

BACKGROUND
Accepted Article Chronic pain ranks as the fifth leading cause of years lived with disability (Vos et al.,
2012). There is a large variety of chronic pain conditions, ranging from arthritis to primary chronic
pain syndromes (Ossipov and Porreca, 2006). Several chronic pain conditions can be situated
along a continuum in which the predominant pain mechanism is widely responsible for the chronic
pain. Distinct mechanisms have different clinical presentations and require a tailored approach.
The main types of pain mechanisms described are: neuropathic, nociceptive, and nociplastic pain
(Chimenti et al., 2018; International Association for the Study of Pain (IASP), 2017 [update from
2012]). Nociplastic pain involves altered nociception despite no clear evidence of actual or
threatened tissue damage leading to the activation of peripheral nociceptors or evidence of disease
or lesion in the somatosensory system (Chimenti et al., 2018; International Association for the
Study of Pain (IASP), 2017 [update from 2012]). Nociplastic pain can be observed in clinical
conditions characterized by evidence of altered nociceptive processing, spread of hypersensitivity,
and altered descending pain inhibition (Kosek et al., 2016). Such presentation includes
manifestations of central sensitization, which may help to explain the phenomena that maintain
and, possibly, increase pain intensity in several clinical conditions.
Quantitative sensory tests are commonly used to assess pain phenomena associated with
central sensitization (Meeus et al., 2015). However, from a clinical point of view, sensitization
may be inferred indirectly from phenomena such as hyperalgesia or allodynia (International
Association for the Study of Pain (IASP), 2017 [update from 2012]). Central sensitization may be
involved in the development of pain in patients when an obvious source of nociception is absent,
may contribute to the transition from acute to chronic pain (Nijs et al., 2014; Sterling et al., 2003),
and also may mediate treatment responses (Coombes et al., 2012; Jull et al., 2007; Nijs et al.,
2014). Patients with central sensitization report severe pain, long pain duration, several number of
painful areas, more widespread pain, poor general health-related quality of life, and high levels of
pain-related disability, depression, and anxiety (Nogueira et al., 2016; Smart et al., 2012).
Some examples of painful conditions with different predominance of nociplastic pain
include fibromyalgia, chronic whiplash-associated disorders (CWAD), and chronic idiopathic
neck pain (CINP). In fibromyalgia, due to the absence of tissue pathology, structural abnormality,
or a clear source of chronic stimulation of pain afferents (Simms et al., 1994), central sensitization
represents the most prominent hypothesis of the pathophysiological mechanism to explain
widespread pain (Häuser et al., 2015). Meanwhile, CWAD is a painful condition that may involve

both peripheral and central sensitization. A systematic review (van Oosterwijck et al., 2013)
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presents evidence that the central nervous system (CNS) is hypersensitized in patients with
CWAD, and that central sensitization plays a crucial role in the persistence of pain. Finally, some
chronic pain conditions rarely show signs of central sensitization such as CINP (Coppieters et al.,
2017; Malfliet et al., 2015). Patients with CINP present recurrent pain, but CINP is more episodic
in nature (Guzman et al., 2008) and leads to interruptions in the nociceptive input. These
characteristics may prevent the development of the pathophysiological processes in the CNS
involved in central sensitization (Malfliet et al., 2015).
Despite the differences in clinical manifestation and pain mechanism, physical exercise is
recommended as a treatment for all of these three chronic conditions (Busch et al., 2013; Bussières
et al., 2016; Fitzcharles et al., 2013; Häuser et al., 2017; Macfarlane et al., 2016; TRACsa: Trauma
and Injury Recovery, 2008). Even with the existing evidence regarding the improvement of
clinical outcomes, the literature is scarce on the parameters for the prescription of therapeutic
exercises and on whether these parameters should be different depending on the predominance of
nociplastic pain. The current evidence from reviews and guidelines regarding weekly frequency
and intensity of exercise prescription (Booth et al., 2017; Bussières et al., 2016; Geneen et al.,
2017; Häuser et al., 2010) encompasses chronic pain in general, without taking into account
specific characteristics or pain mechanism of each painful condition. Thus, the recommendation to
prescribe exercise programs is varied and generic for patients with chronic pain. Additionally,
exercise prescription is often dependent on the clinician's individual preferences and abilities.
Together, these facts may contribute to the underestimation or overestimation of exercise
prescription parameters in specific chronic pain conditions (Booth et al., 2017). Considering that
patients with nociplastic pain usually have dysfunctional endogenous analgesic control, which
contributes to exercise-induced hyperalgesia (Lima et al., 2017; Meeus et al., 2016), and that
exercise prescription can directly influence the outcomes of an intervention, it is important to
synthetize the evidence about exercise parameters in the prescription for patients with painful
conditions in the continuum of nociplastic pain. Thus, the aim of this study was to systematically
review the effects of different exercise prescriptions and synthetize the exercise parameters for
pain management in patients with chronic pain along the continuum of nociplastic pain:
fibromyalgia (situated at the end of the continuum), CWAD (different degrees of predominance of
nociplastic pain), and CINP (nociplastic pain is not a dominant feature).

METHODS
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Protocol registration
The present systematic review was reported following the Preferred Reported Items for
Systematic Reviews and Meta-analyses (PRISMA) statement (Moher et al., 2009). The systematic
review protocol was prospectively registered in the Prospero website (CRD42019123271).
Eligibility criteria
The inclusion criteria for this systematic review were: 1) randomized controlled trials
(RCTs); 2) studies with patients over 18 years of age with fibromyalgia who were diagnosed by
the American College of Rheumatology criteria of 1990, 2010, 2011, or 2016 (Wolfe et al., 2016;
Wolfe et al., 2011; Wolfe et al., 2010; Wolfe et al., 1990); or patients over 18 years of age who
suffered from a chronic whiplash injury (more than 12 weeks) classified as CWAD grade 1 and 2
(Grade 1 - neck complaints, such as pain, tenderness, and stiffness, but no physical signs; Grade 2
- neck complaints with musculoskeletal signs, such as decreased range of motion or muscle
weakness (Spitzer, 1995)), because these patients normally receive conservative interventions
(Bussières et al., 2016; TRACsa: Trauma and Injury Recovery, 2008; Verhagen et al., 2007); or
studies with patients over 18 years of age with CINP (more than 12 weeks); 3) at least two
physical exercise interventions to control pain should be prescribed. Exercise was defined as a
planned, structured, and repetitive physical activity (Caspersen et al., 1985)); and 4) studies with a
minimum duration of 3 weeks of exercise.
The exclusion criteria were: 1) studies in which exercise was a component of a multimodal
treatment; 2) studies that only included a single bout of exercise, but not an exercise program; 3)
studies in which patients with fibromyalgia, CWAD, and CINP had recently undergone surgery or
suffered a new acute neck injury; 4) studies in which patients with CINP had other comorbidities
(such as shoulder pain, temporomandibular disorders, radiculopathies, among others); and 5)
studies that did not describe any parameters of the prescribed exercises.
Search strategy
Systematic electronic searches were carried out in the following databases: Cochrane
Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, Cumulative
Index to Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence Database
(PEDro) from inception until November 19th, 2018. An additional hand search was performed in
the references of pre-selected articles for inclusion in this review and in systematic reviews and

clinical guidelines published on each condition (Bidonde et al., 2017; Busch et al., 2013; Bussières
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et al., 2016; Gross et al., 2015; Häuser et al., 2010; Macfarlane et al., 2016; O'Riordan et al., 2014;
Sosa-Reina et al., 2017; Verhagen et al., 2007). Searches were not restricted by language or
publication date.
The terms used in the searches were based on the strategies proposed by the Updated
Search Strategies of the Cochrane Group (van Tulder et al., 2003) and systematic reviews on the
topic (Bidonde et al., 2017; Busch et al., 2013; Gross et al., 2015; Verhagen et al., 2007). To
systematize the searches, six thematic blocks were constructed with synonyms and variants related
to chronic pain, fibromyalgia, neck pain, whiplash, exercise, and outcomes. In addition, filters
were used to include only randomized controlled trial and humans (Appendix 1). The words
within a block were combined by the Boolean operator "OR" and between blocks by the Boolean
operator "AND".
Data extraction
Two assessors (KFMF and DL) conducted, independently, the selection of the studies, data
extraction of the included studies, and analysis of the methodological quality. In cases of
disagreement, a third assessor (MM) made the final decision.
Risk of bias assessment

The risk of bias of the eligible studies was analyzed using the criteria from the Cochrane
Risk of Bias tool with seven items (Higgins and Green, 2011). Each item was scored as ‘yes’,
‘no’, or ‘unclear’. Studies that met at least three or more of the seven criteria were considered as
having a low risk of bias. In studies with an exercise intervention, blinding of participants and care
providers is not possible (Busch et al., 2013). Thus, a low risk was assumed when participants
were kept unaware of other treatment arms, a high risk was assumed when authors clearly stated in
the text that participants were not blinded to intervention, and an unclear risk was assumed when
no information on blinding of participants was reported.
Quality of the evidence

Two assessors (KFMF and YRSF) rated the quality of the evidence using the GRADE
approach (Schünemann et al., 2011) via the GRADE PRO website. The large heterogeneity
prevented the pooling of similar studies. Therefore, the quality of the evidence was only

performed for pain and for studies included in the meta-analyses and was described along with
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these results. The GRADE approach proposes domains to assess the quality of the body of
evidence for each outcome. The criteria used were: 1) risk of bias (downgraded if more than 25%
of the participants were from studies with a high risk of bias); 2) inconsistency of results
(downgraded if significant heterogeneity was presented considering I² > 50%); 3) indirectness
(downgraded if more than 50% of the participants or interventions were outside of interest); 4)
imprecision (downgraded if less than 400 participants were included in the comparison); and 5)
other (for example, publication bias) (Balshem et al., 2011; Higgins and Green, 2011;
Schünemann et al., 2011). For each domain that did not meet the criterion, quality was
downgraded by one level, from high to moderate, low or very low quality. Based on these criteria,
the GRADE approach assigns grades of evidence per cluster ranging from high to very low level
of evidence (Balshem et al., 2011).
Data extraction and analysis

The primary outcome was the effect of any exercise parameter prescription (type of
exercise, duration, frequency, number of sets, number of repetitions, rest time between sets and
between sessions, initial load, intensity, progression of load, clinical criteria used for progression,
and criteria for the change of exercise in case of non-progression, among others) on pain intensity.
Secondary outcomes were the effect of any exercise parameter on disability, impact of
fibromyalgia, quality of life, satisfaction with treatment, and adverse effects of physical exercise in
patients with fibromyalgia, CWAD, and CINP.
Data extraction forms encompassed the following information from the studies: 1) authors
and year of publication; 2) aim of the study; 3) characteristics of the sample (sample size, age, sex,
weight, height, body mass index, and duration of symptoms); 3) physical exercise parameters from
the experimental group; 4) physical exercise parameters from the comparison group; 5) outcome
measures; 6) instruments used to assess outcomes; 7) follow-up (short-term: between 3 and 23
weeks; medium-term: between 24 and 51 weeks; and long-term: more than 52 weeks (Furlan et
al., 2015)); and 8) study results, i.e. mean and standard deviation (SD) values (or median and
interquartile range) of each group, mean difference (MD), confidence intervals at 95% (95% CI),
effect size for the comparisons between groups, and whether the intervention effect was minimally
important for pain (between 10% and 20% or 10 mm in the visual analogue scale - VAS)
(Dworkin et al., 2008). When the between-group results were not presented, we used the means

and standard deviations (or medians and interquartile ranges) of each group to calculate the MD
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and 95% CI between the groups using the RevMan calculator (RevMan 5.3). The analysis of the
studies was clustered based on the categories of physical exercise.
Data analysis
A meta-analysis was only performed for the primary outcome (pain intensity) at short-term
follow-up (Furlan et al., 2015; Geneen et al., 2017) and was conducted using the Review Manager
Analysis software (RevMan 5.3) from the Cochrane Collaboration. We used MDs with 95% CIs
for continuous data (Higgins and Green, 2011). MDs were calculated from the means and SDs of
each intervention, except for the comparison “high-intensity aerobic vs low-intensity aerobic
exercise” for fibromyalgia, because the included studies only provided within-group difference
values. The combined results were assessed using a random-effects model, which is more
conservative than a fixed-effects model, and incorporates both within- and between-study
variance. Overall effects were assessed using the 𝑍 statistic; 𝑝 < 0.05 allowed the conclusion that a
systematic effect had been demonstrated (Sosa-Reina et al., 2017). Heterogeneity was assessed
using the 𝐼2 statistic, interpreted as follows: 𝐼2 < 40%, might not represent important heterogeneity;
𝐼2 = 30–60%, may represent moderate heterogeneity; 𝐼2 = 50–90%, may represent substantial
heterogeneity; and 𝐼2 = 75–100%, considerable heterogeneity (Higgins and Green, 2011).
When data were not extractable, the primary authors were contacted. Continuous outcomes
reported as medians, interquartile range, and range were transformed into mean and standard
deviation using RevMan 5.3 (Higgins and Green, 2011; Hozo et al., 2005).
RESULTS
Study selection
The search strategy returned 1,413 articles. After exclusion of duplicates, screening of title
and abstracts, and reading the full texts, 50 RCTs were included in the descriptive synthesis. Only
24 studies were included in the quantitative analyses due to differences between interventions.
Three studies were excluded because they were published in a language that could not be
translated (Turkish (Yuruk and Gultekin, 2008), Persian (Arami et al., 2012), and Finnish (Ylinen
et al., 2004)). Details on the search and screening process can be found in Figure 1.
Insert Figure 1 here

Included studies
Accepted Article A total of 3,562 participants were included. Of these, 26 studies (1,649 participants)
examined exercises for patients with fibromyalgia (Assis et al., 2006; Assumpção et al., 2018;
Bircan et al., 2008; Bjersing et al., 2012; Calandre et al., 2009; Demir-Göçmen et al., 2013;
Duruturk et al., 2015; Evcik et al., 2008; Fernandes et al., 2016; Gavi et al., 2014; Genc et al.,
2015; Jentoft et al., 2001; Jones et al., 2002; Kayo et al., 2012; Mannerkorpi et al., 2010; McCain
et al., 1988; Nørregaard et al., 1997; Ramsay et al., 2000; Richards and Scott, 2002; Rooks et al.,
2007; Sañudo et al., 2010; Schachter et al., 2003; Sevimli et al., 2015; Valim et al., 2003; van
Santen et al., 2002; Wang et al., 2018), two studies (326 participants) examined exercises for
patients with CWAD (Seferiadis et al., 2016; Vikne et al., 2007), and 22 studies (1,587
participants) examined exercises for patients with CINP (Andersen et al., 2008; Bobos et al., 2016;
Borisut et al., 2013; Cramer et al., 2013; Falla et al., 2006; Häkkinen et al., 2008; Izquierdo et al.,
2016; Javanshir et al., 2015; Karlsson et al., 2014; Khan et al., 2014; Kietrys et al., 2007; Kim and
Kwag, 2016; Lansinger et al., 2013; Lansinger et al., 2007; Lauche et al., 2016; O'Leary et al.,
2012; Rendant et al., 2011; Salo et al., 2012; Salo et al., 2010; Senthil et al., 2016; von Trott et al.,
2009; Ylinen et al., 2003). The results are presented by clinical condition.
General characteristics of the studies

Patients with fibromyalgia had a mean age of 45.8 years, and only 36 patients (2.2%) were
male. Aerobic exercise was tested in 28 treatment groups (Assis et al., 2006; Bircan et al., 2008;
Bjersing et al., 2012; Duruturk et al., 2015; Fernandes et al., 2016; Genc et al., 2015; Jentoft et al.,
2001; Kayo et al., 2012; Mannerkorpi et al., 2010; McCain et al., 1988; Nørregaard et al., 1997;
Ramsay et al., 2000; Richards and Scott, 2002; Sañudo et al., 2010; Schachter et al., 2003; Sevimli
et al., 2015; Valim et al., 2003; van Santen et al., 2002; Wang et al., 2018), including walking,
exercise on a cycle ergometer/bicycle, exercise on a treadmill, land-based or water-based exercise,
or exercise with high and low intensity. Muscle strengthening was tested in five treatment groups
(Assumpção et al., 2018; Bircan et al., 2008; Gavi et al., 2014; Jones et al., 2002; Kayo et al.,
2012), stretching in eight (Assumpção et al., 2018; Calandre et al., 2009; Demir-Göçmen et al.,
2013; Gavi et al., 2014; Genc et al., 2015; Jones et al., 2002; McCain et al., 1988; Valim et al.,
2003), a combination of different types of exercise in nine (Demir-Göçmen et al., 2013; Evcik et
al., 2008; Nørregaard et al., 1997; Richards and Scott, 2002; Rooks et al., 2007; Sañudo et al.,

2010; Sevimli et al., 2015), Tai Chi in two (Calandre et al., 2009; Wang et al., 2018), and balance
Accepted Article
exercises in one treatment group (Duruturk et al., 2015).
Patients with CWAD had a mean age of 48.0 years, and only one study reported
demographic data (Seferiadis et al., 2016). In this study, 32 (28.3%) of the 113 participants were
male (Seferiadis et al., 2016). One study compared different types of exercise (strengthening,
aerobic, and coordination) with body awareness exercises (Seferiadis et al., 2016), and the other
study compared the combination of muscle strengthening and endurance with the addition of sling
exercises to the same combination (Vikne et al., 2007).
Patients with CINP had a mean age of 42.8 years, and approximately 139 participants
(8.7%) were male. Muscle strengthening (strength exercise, endurance, or both) was tested in 12
treatment groups (Bobos et al., 2016; Borisut et al., 2013; Javanshir et al., 2015; Karlsson et al.,
2014; Khan et al., 2014; Kietrys et al., 2007; Kim and Kwag, 2016; O'Leary et al., 2012; Salo et
al., 2010; Ylinen et al., 2003). Motor control exercises were examined in nine treatment groups
(Andersen et al., 2008; Bobos et al., 2016; Borisut et al., 2013; Falla et al., 2006; Izquierdo et al.,
2016; Javanshir et al., 2015; Kim and Kwag, 2016; O'Leary et al., 2012; Senthil et al., 2016),
stretching in four (Häkkinen et al., 2008; Karlsson et al., 2014; Kietrys et al., 2007; Salo et al.,
2012), a combination of different types of exercises in nine (Cramer et al., 2013; Häkkinen et al.,
2008; Lansinger et al., 2013; Lansinger et al., 2007; Lauche et al., 2016; Rendant et al., 2011; Salo
et al., 2012; Senthil et al., 2016; von Trott et al., 2009), specific techniques (Qigong, Tai Chi and
Yoga) in six (Cramer et al., 2013; Lansinger et al., 2013; Lansinger et al., 2007; Lauche et al.,
2016; Rendant et al., 2011; von Trott et al., 2009), and aerobic exercise (Andersen et al., 2008),
active range of motion exercises (Khan et al., 2014) and proprioceptive exercises (Izquierdo et al.,
2016) in one treatment group each.
Risk of bias
Results on the risk of bias assessment are provided in Figures 2 and 3. In general, the
studies presented a low risk of bias. High risk of bias and uncertainty were identified in the
categories allocation and blinding of participants (Figures 2a, 2b and 2c).
Twelve studies presented high risk of bias considering incomplete outcome data (eight in
fibromyalgia (Assis et al., 2006; Calandre et al., 2009; Gavi et al., 2014; Jentoft et al., 2001;
Nørregaard et al., 1997; Schachter et al., 2003; Valim et al., 2003; van Santen et al., 2002) and

four in CINP (Andersen et al., 2008; Häkkinen et al., 2008; Lansinger et al., 2013; Salo et al.,
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2012)), because these studies had different dropout rates between groups, did not use intention-to-
treat analysis, or used non-recommended imputation methods (Figure 3). The assessment of
selective reporting bias was difficult because only one research protocol was available (Wang et
al., 2015). Nine studies, six in fibromyalgia (Kayo et al., 2012; Mannerkorpi et al., 2010; Richards
and Scott, 2002; Rooks et al., 2007; Sañudo et al., 2010; Sevimli et al., 2015) and three in CINP
(Kietrys et al., 2007; Salo et al., 2010; Ylinen et al., 2003), were rated as having a high risk of
selective reporting (Figure 3). These studies did not analyze the between-group difference after
treatment or follow-ups, which is usually the main analysis of RCTs. There was no other potential
risk of bias in the included studies and therefore the risk due to other sources was rated as low.
Effects of intervention
Meta-analyses for pain intensity at short-term follow-up were performed for fibromyalgia
and CINP, and the results will be presented below. Other data can be found in Supplementary File
1 (characteristics of the included studies are presented in Supplementary Table 1, details on
exercise prescription in each treatment group in Supplementary Table 2, and the quality of
evidence in Supplementary Table 3) and Supplementary File 2 (descriptive data for fibromyalgia
and CINP studies). Descriptive results related to CWAD will be presented in the text because it
was not possible to perform any meta-analyses.
Exercise prescription parameters for fibromyalgia

Type of therapeutic exercise
Aerobic exercise versus Muscle strengthening
For this comparison, a meta-analysis with two studies (Bircan et al., 2008; Kayo et al.,
2012) showed low-quality evidence of no difference between aerobic exercises and muscle
strengthening for pain reduction [MD: 2.0 mm; 95% CI: -4.6 to 8.6; assessed using Visual
analogue scale (VAS), 0 to 100 mm] (Figure 4a).
Aerobic exercise versus Muscle stretching

Accepted Article A meta-analysis with three studies (Genc et al., 2015; McCain et al., 1988; Valim et al.,
2003) showed low-quality evidence of a small effect of aerobic exercise on pain reduction [MD: -
8.1 mm; 95% CI: -15.2 to -0.9; assessed using VAS, 0 to 100 mm] (Figure 4b).
Land-based aerobic exercise versus Water-based aerobic exercise

A meta-analysis with four studies (Assis et al., 2006; Fernandes et al., 2016; Jentoft et al.,
2001; Sevimli et al., 2015) showed very low-quality evidence of no difference between exercises
performed on land or in water for pain reduction [MD: -3.0 mm; 95% CI: -11.3 to 5.2; assessed
using VAS, 0 to 100 mm] (Figure 4c).
Muscle strengthening versus Muscle stretching

A meta-analysis with three studies (Assumpção et al., 2018; Gavi et al., 2014; Jones et al.,
2002) showed low-quality evidence of a small effect of muscle strengthening on pain reduction
compared to muscle stretching [MD: -7.0 mm; 95% CI: -8.1 to -5.8; assessed using VAS, 0 to 100
mm] (Figure 4d).
Supervised exercises
A meta-analysis with five studies and six comparisons (Demir-Göçmen et al., 2013; Evcik
et al., 2008; Genc et al., 2015; Ramsay et al., 2000; Sevimli et al., 2015) showed very low-quality
evidence of a superior and clinically relevant effect of supervised exercises on pain reduction
compared to unsupervised exercises [MD: -10.0 mm; 95% CI: -19.6 to -0.3; assessed using VAS,
0 to 100 mm]. The heterogeneity of this meta-analysis was very high (I² = 90%) because different
types of exercise were included (Figure 4e).
Intensity of the exercise

A meta-analysis with three studies (Bjersing et al., 2012; Mannerkorpi et al., 2010; van
Santen et al., 2002) showed low-quality evidence of no difference between high and low intensity
aerobic exercises for pain reduction [MD: -1.1 mm; 95% CI: -8.0 to 5.9; assessed using VAS, 0 to
100 mm] (Figure 4f).
Adverse effects of exercise

Accepted Article The following adverse effects were reported during aerobic exercise: transient knee pain
(McCain et al., 1988), minor musculoskeletal events (Wang et al., 2018), and increase in pain
intensity during high-intensity aerobic exercise (van Santen et al., 2002). Furthermore, muscle
pain during land-based aerobic exercise was more frequently reported than during water-based
aerobic exercise (Assis et al., 2006). An adverse effect during muscle strengthening exercise was
worsening of pain (Assumpção et al., 2018; Jones et al., 2002). During stretching exercise, adverse
effects reported were worsening of pain (Jones et al., 2002) and Achilles tendinitis (McCain et al.,
1988). During Tai Chi, worsening of pain (Calandre et al., 2009) and minor musculoskeletal
events (Wang et al., 2018) were reported. All these adverse effects were reported in a small
number of patients (details in Supplementary File 1, Supplementary Table 1).
Exercise prescription parameters for chronic whiplash-associated disorders

Body awareness exercise versus Combined exercise
One study (Seferiadis et al., 2016) showed no difference between body awareness exercise
and combined exercise (aerobic plus strengthening plus coordination exercises) for pain and
disability in the short-term. However, body awareness exercises were superior for quality of life in
the short-term.
Combined exercise versus other Combined exercise

One study (Vikne et al., 2007) showed no difference between sling exercise plus
strengthening plus endurance exercises and a program of strengthening plus endurance exercises
for pain and disability in the short- and long-term.
Supervised exercises
All included studies (Seferiadis et al., 2016; Vikne et al., 2007) used supervised exercise.
One study added unsupervised exercise for the period of 32 weeks after the supervised
intervention (Vikne et al., 2007) and showed that exercising at home had no additional effect on
pain and disability management.
Duration of the session

Accepted Article Only one study (Seferiadis et al., 2016) reported the duration of the exercise session, which
was 90 minutes of body awareness exercises or aerobic plus strengthening plus coordination
exercises per session.
Weekly treatment frequency

One study (Seferiadis et al., 2016) reported that the weekly frequency of exercise sessions
was twice a week.
Duration of treatment
One study (Seferiadis et al., 2016) conducted the treatment for 10 weeks, while the other
(Vikne et al., 2007) conducted supervised therapy for 16 weeks, and the two groups also
conducted 32 weeks of the same therapy at home.
Intensity of the exercise

Neither of the included studies (Seferiadis et al., 2016; Vikne et al., 2007) reported the
intensity of the exercises.

Worsening of pain was reported in both body awareness and combined exercises
(Seferiadis et al., 2016) in a small number of patients (details in Supplementary File 1,
Supplementary Table 1).
Exercise prescription parameters for chronic idiopathic neck pain

Muscle strengthening versus Motor control
Six studies compared motor control exercises to muscle strengthening. Two studies
(Borisut et al., 2013; Falla et al., 2006) compared motor control exercises to a combination of
muscle strength and muscle endurance exercises, and four studies (Bobos et al., 2016; Javanshir et
al., 2015; Kim and Kwag, 2016; O'Leary et al., 2012) compared motor control exercises to
nonspecific strengthening of the neck muscle; however, one of these studies (Bobos et al., 2016)
did not provide enough information to be included in the meta-analysis. Therefore, a meta-analysis
of the three remaining studies (Javanshir et al., 2015; Kim and Kwag, 2016; O'Leary et al., 2012)

was carried out and showed very low-quality evidence of no difference between motor control
Accepted Article
exercises and nonspecific strengthening of the neck muscles for pain reduction [MD: -3.2 mm;
95% CI: -13.8 to 7.5; assessed using VAS, 0 to 100 mm] (Figure 5a).
Mind-body exercises (Qigong and Tai Chi) versus Combined exercise

A meta-analysis of three studies (Lansinger et al., 2007; Lauche et al., 2016; von Trott et
al., 2009) showed low-quality evidence of a small effect of several combined exercise modalities
(aerobic, strengthening, stretching, active range of motion, and proprioceptive exercises) on pain
reduction [MD: 6.5 mm; 95% CI: 0.8 to 12.2; assessed using VAS, 0 to 100 mm] (Figure 5b).

During Yoga, minor adverse events, pain worsening, and muscle soreness were reported
(Cramer et al., 2013). During Tai Chi, migraine and Achilles tendon pain were reported (Lauche et
al., 2016). During Qigong, muscle soreness, myogelosis (painful change in muscle structure
correlated with the myofascial trigger points (Windisch et al., 1999)), other pain, neck twinge,
headache, and vertigo/nausea were reported (Rendant et al., 2011; von Trott et al., 2009). During
combined exercises, knee pain and vertigo were reported (Lauche et al., 2016), as well as
worsening of neck pain and tinnitus, muscle soreness, myogelosis, headache, and vertigo/nausea
(Rendant et al., 2011; von Trott et al., 2009). All these adverse effects were reported in a small
number of patients (details in Supplementary File 1, Supplementary Table 1).
A summary of the exercise prescriptions recommended for each condition is presented in
Table 1.
Insert Table 1 here
DISCUSSION
Summary of the main results
The aim of this systematic review was to compare the effects of different exercise
prescriptions for pain management in patients with chronic pain along the continuum of
nociplastic pain (represented by patients with fibromyalgia, CWAD, and CINP). Effect sizes
found were generally below the minimal clinically important difference threshold of 20% or 10

mm. There was very low- to low-quality of evidence, using the GRADE approach, creating a high
Accepted Article
degree of uncertainty in these results. The main findings of this systematic review were:
Fibromyalgia
Aerobic exercise and muscle strengthening showed similar small effects, but both exercises
were better than stretching exercises alone. Apparently, there was no difference between
performing land or pool-based aerobic exercise or aerobic exercise at low or high intensity.
Supervised exercises were a little better than unsupervised exercises. The majority of exercise
sessions for patients with fibromyalgia were performed for 50 to 60 minutes, 2 to 3 times a week,
for a period of 13 to 24 weeks of treatment. Intensity of the aerobic exercises were set at 40% to
80% of the maximal heart rate or at a perceived exertion between 9 to 15 on the Rated Perceived
Exertion scale. The intensity of muscle strengthening was 45 to 50% of 1 repetition maximum and
stretching was performed until the patient experienced moderate discomfort.
Chronic whiplash associated disorder
Body awareness exercises had similar effects to the combination of aerobic + strengthening
+ coordination exercises. There was no difference in adding sling exercises to the combination of
muscle strengthening + muscle endurance exercises. Regarding exercise prescription, the exercises
were supervised in 90-minute sessions, twice a week, for a period of 10 to 16 weeks.
Chronic idiopathic neck pain
Motor control exercises were similar to nonspecific muscle strengthening, but combined
exercise was better than meditative therapies (Tai Chi and Qigong). The majority of the exercises
were performed in a supervised manner, in sessions of 30 to 60 minutes duration, 2 to 3 times a
week, for a period of 7 to 12 weeks of treatment. Regarding exercise intensity, aerobic exercises
were performed at 50% to 75% of the VO2max, muscle strengthening at 20 to 80% of the
maximum voluntary contraction/maximal isometric contraction or between 15 to 8 maximal
repetitions, and motor control exercises with isometric contractions of 10 seconds and an inflated
pressure biofeedback device at 20 to 33 mmHg.
Similarities and discrepancies with other studies or reviews
The literature shows that interventions based on physical exercise have a beneficial effect
on the treatment of chronic pain (Booth et al., 2017; Geneen et al., 2017). Thus, knowledge about
the best type of exercise and prescription for patients with chronic pain is extremely important.
Currently, the major challenge for clinicians is to correctly tailor exercise to maximize clinical
effect without exacerbating symptoms. Regarding exercise prescription for patients with chronic

pain in general, a previous clinical update (Booth et al., 2017) recommended that aerobic exercises
Accepted Article
be performed for 20 to 60 minutes, twice a week, for a minimum of 6 weeks, with mild to
moderate intensity (40 to 70% of maximum heart rate [HRmax]). For strengthening exercises, the
same study recommended one to two sets of 15 to 20 repetitions, 2 to 3 times a week, for at least 6
weeks, with mild to moderate intensity (40 to 60% 1 Repetition maximum [RM]). Some of these
findings were similar to ours. However, our results showed that, for patients with fibromyalgia and
CINP, exercise intensity can be higher than previously recommended, taking care to increase
intensity gradually (40% to 80% HRmax for fibromyalgia, and 50% to 75% of VO2max for
CINP).
One study (Polaski et al., 2019) assessed factors related to exercise prescription that could
influence the improvement of pain in chronic health conditions and showed that, when exercise
frequency per week was increased, a substantial increase in analgesic effect was found. However,
when the duration of exercise (expressed in minutes per week) or duration of the study was
increased, the model predicted a decrease in analgesic effect. In the present study, a meta-analysis
for weekly frequency and duration of treatment could not be performed. Nevertheless, we
observed an ideal frequency of 2 to 3 times a week in most of the included studies. In addition, we
observed that treatment for painful conditions with predominance of central sensitization should
last longer (at least 10 to 13 weeks for patients with CWAD and fibromyalgia) than treatment for
painful conditions without nociplastic pain (at least 7 weeks for CINP).
None of the previous studies considered the central sensitization for exercise prescription.
Currently, there are few methods to assess patients who present central sensitization characteristics
in clinical practice. Current evidence suggests that the qualitative tests and the Central
Sensitization Inventory (Mayer et al., 2012; Neblett et al., 2013) are the main clinical criteria for
the classification of central sensitization pain (Nijs et al., 2014). In addition, some aspects related
to central sensitization, such as dysfunctional endogenous analgesic control, can be quantitatively
assessed using the conditioned pain modulation and temporal summation tests, and hyperalgesia
can be assessed using an algometer (pressure pain threshold) (Meeus et al., 2015). With this
information, the therapist can assess whether the patient's pain has a nociceptive or nociplastic
predominance, and thus, prescribe an adequate exercise program. In fact, the investigation of
central sensitization should be considered in clinical practice before exercise prescription
(Chimenti et al., 2018; Nijs et al., 2012) given that patients with painful conditions with
predominance of central sensitization probably have dysfunctional endogenous analgesia, which

might predispose them to exercise-induced hyperalgesia (Nijs et al., 2012). In these cases, a
Accepted Article
narrative review (Nijs et al., 2012) suggests the following strategies to prevent exercise-induced
hyperalgesia: 1) Prescription of aerobic exercise and motor control training, as well as caution
with eccentric exercise; 2) Inclusion of exercise for non-painful areas; 3) Allowing a small
increase in pain during exercise, but avoiding a continuous increase in pain intensity over time and
changing the exercise if pain intensity increases; 4) Use of a time-contingent approach with
appropriate baseline assessment; 5) Opting for a conservative baseline; and 6) Use of multiple and
long recovery breaks between exercises.
Some of these strategies were observed in the results of the present review, such as the
prescription of aerobic and more general exercises and a progression of exercise based on time-
contingent approach, being careful with any increase in pain intensity for the majority of the
studies with patients with fibromyalgia. These observed strategies show that general exercises may
be performed without pain exacerbation (Chimenti et al., 2018; Lannersten and Kosek, 2010; Nijs
et al., 2012). In contrast, studies on CINP, the health condition without predominance of
nociplastic pain, prescribed exercises focusing only on the neck area and with high intensity. By
adding more specific exercises to the treatment, the therapist can improve the central effect
generated by the exercise, while also generating local effects on muscles and joints (Andersen et
al., 2008; Meeus et al., 2016). In the studies that assessed CWAD, the prescription depended on
the predominance of nociplastic pain presented by the patient. These results show that these
characteristics can now be used as a basis for a more individualized prescription.
Strengths and weaknesses

The recommendations made by this systematic review are based on very low- to low-
quality evidence, mainly because of the low number of studies comparing different aspects of
exercise prescription, the heterogeneity of the intervention protocols, and the low number of
patients assessed. These factors resulted in great heterogeneity and small sample sizes for the
comparisons and indicate that further studies are necessary. Moreover, the included studies
presented poor description of the exercise parameters, which hindered data extraction. Many RCTs
did not perform between-group comparisons and did not provide data for each group at each
treatment time, hampering the performance of proper meta-analyses.
As a strength, this systematic review included only RCTs in which the comparison groups
were composed of physical exercise in order to assess whether the prescribed exercise parameters

would influence patient-centered clinical outcomes. Meta-analyses of all possible comparisons
Accepted Article
were performed, which provides more accurate and specific quantitative results. Another strength
of our study is that we described the results highlighting the clinical relevance of the effect sizes
found in the meta-analyses, which provides the clinical significance of the results for the clinician
and, most importantly, for the patient. In addition, this systematic review provides relevant
information to clinical practice because we extensively summarized the available evidence on each
aspect of exercise prescription per conditions of chronic pain along the continuum of nociplastic
pain, which is a current and highly relevant topic.
Implications for practice

For pain conditions with predominance of nociplastic pain (i.e. fibromyalgia), clinicians
should consider prescribing aerobic, muscle strengthening, and mind-body exercises (i.e. Qigong
or Tai Chi). Supervised sessions with 50- to 60-minute duration, 2 to 3 times a week, for 13 weeks
or more are recommended. For pain conditions with varying degrees of predominance of
nociplastic pain (as CWAD), clinicians may mix general and specific neck exercises. Supervised
sessions performed twice a week for up to 90 minutes, for 10 to 16 weeks can be prescribed.
Finally, for pain conditions without predominance of nociplastic pain (as CINP), motor control
and muscle strengthening exercises may be considered by clinicians. Supervised sessions with 30-
to 60-minute duration, 2 to 3 times a week, for a period of 7 to 12 weeks of treatment are
recommended. The results of this review may aid in the exercise prescription for other pain
conditions as well, considering the situation within the continuum of nociplastic pain.
Implications for research
To increase the quality of the evidence, more studies comparing different parameters of
exercise prescription with larger samples are recommended. Additionally, adequate recording and
description of the types and exact dosage of the exercise programs are also important to facilitate
translation into clinical practice, as well as for the pooling of data to improve the directness of the
outcomes. Therefore, we recommend the use of the guidelines by the Template for Intervention
Description and Replication (TIDieR), which guides the best way to report interventions (Yamato
et al., 2016). It is of the utmost importance that authors follow the CONSORT guidelines (Schulz
et al., 2010) and do not fail to perform between-group comparison analyses.
CONCLUSION

Accepted Article This systematic review found that there is no difference between the majority of exercises
for pain reduction, considering the health conditions included in this review. Regarding
fibromyalgia, aerobic and muscle strengthening exercises are slightly superior to isolated
stretching exercises, which can be performed in supervised sessions with 50- to 60-minute
duration, 2 to 3 times a week, for a treatment period of 13 weeks or more. For CWAD, body
awareness exercises and combined exercises (aerobic plus strengthening plus coordination
exercises) can be prescribed, and the addition of sling exercises to a combination of strength plus
endurance exercises does not provide additional effects. The exercises can be performed in
supervised sessions, twice a week for up to 90 minutes, for a treatment period of 10 to 16 weeks or
more. Finally, for CINP, motor control, nonspecific muscle strengthening, and a combination of
strengthening plus endurance exercises can be prescribed, with combined exercises (aerobic,
strengthening, stretching, active range of motion, proprioceptive exercises) being slightly superior
to mind-body exercises. The exercises can be performed in supervised sessions with 30- to 60-
minute duration, 2 to 3 times a week, for a period of 7 to 12 weeks.
AUTHOR CONTRIBUTIONS
Katherinne Franco, Mira Meeus, Cristina Cabral, and Felipe Reis developed the study.
Katherinne Franco, Dorine Lenoir, and Yuri Franco collected the data. Katherinne Franco and
Yuri Franco performed the meta-analysis. All authors contributed to the improvement of the
paper, approved the manuscript, and agreed with its submission to the European Journal of Pain.
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APPENDIX 1 - Search strategy
Accepted Article
MEDLINE (Pubmed) search strategy
(((((chronic pain OR "Chronic Pain"[Mesh] OR long-lasting pain OR persisting pain OR long-
term pain) AND (((idiopathic OR aspecific OR non-specific OR non-traumatic) AND (neck pain
OR neckache OR cervical pain OR Cervical disorder* OR "Neck Pain"[Mesh])) OR fibromyalgia
OR fibrositis OR "myofascial pain syndromes"[Mesh] OR "Fibromyalgia"[Mesh] OR whiplash
OR whiplash injuries OR "Whiplash Injuries"[Mesh] OR whiplash associated disorders) AND
(exercise OR exercise therap* OR "Exercise Movement Techniques"[Mesh] OR "Exercise
Therapy"[Mesh] OR "Exercise"[Mesh] OR Rehabilitation[Mesh] OR Rehabilitation OR
Hydrotherapy[Mesh] OR Water therap* OR Physical Fitness OR Physical Endurance OR
Pliability OR "Tai Ji"[Mesh] OR Movement OR rehab OR Run OR Ran OR Running OR Jog OR
Jogging OR Swim* OR swimming OR Walk* OR walking OR cycle* OR cycling OR bicycl* OR
Motor Activit* OR Training* OR Stretch* OR Strengthening OR strength* OR Motion therap*
OR gymnast* OR isometric* OR isotonic* OR isokinetic* OR aerobic* OR physiotherap* OR
kinesiotherap* OR Stabili* OR segment* OR "motor control" OR ((McKenzie OR Alexander OR
William OR Feldenkrais) adj (technique OR method OR methods)) OR Yoga OR Pilates OR
Aerobic exercise* OR Endurance OR Therapeutic exercise*) AND (pain OR "Neck Pain"[Mesh]
OR pain perception OR "Pain Perception"[Mesh] OR pain intensity OR disability OR
functionality OR "Disability Evaluation"[Mesh]OR treatment outcome[Mesh] OR therapy
effect)))))
Limits:
Clinical Study; Clinical Trial; Clinical Trial, Phase I; Clinical Trial, Phase II; Clinical Trial, Phase
III; Clinical Trial, Phase IV; Comparative Study; Controlled Clinical Trial; Randomized
Controlled Trial; Humans
EMBASE search strategy

('chronic pain' OR 'chronic pain'/exp OR 'long-lasting pain' OR 'persisting pain' OR 'long-term
pain') AND ((idiopathic OR aspecific OR 'non specific' OR 'non traumatic') AND ('neck pain'
OR neckache OR 'cervical pain' OR 'cervical disorder*' OR 'neck pain'/exp) OR fibromyalgia
OR fibrositis OR 'myofascial pain syndromes'/exp OR 'fibromyalgia'/exp OR whiplash OR
'whiplash injuries' OR 'whiplash injuries'/exp OR 'whiplash associated disorders') AND (exercise

OR 'exercise therap*' OR 'exercise movement techniques'/exp OR 'exercise therapy'/exp OR
Accepted Article
'exercise'/exp OR 'rehabilitation'/exp OR rehabilitation OR 'hydrotherapy'/exp OR 'water
therap*' OR 'physical fitness' OR 'physical endurance' OR pliability OR 'tai ji'/exp OR
movement OR rehab OR run OR ran OR running OR jog OR jogging OR swim* OR swimming
OR walk* OR walking OR cycle* OR cycling OR bicycl* OR 'motor activit*' OR training* OR
stretch* OR strengthening OR strength* OR 'motion therap*' OR gymnast* OR isometric* OR
isotonic* OR isokinetic* OR aerobic* OR physiotherap* OR kinesiotherap* OR stabili* OR
segment* OR 'motor control' OR ((mckenzie OR alexander OR william OR feldenkrais) AND
adj AND (technique OR method OR methods)) OR yoga OR pilates OR 'aerobic exercise*' OR
endurance OR 'therapeutic exercise*') AND (pain OR 'neck pain'/exp OR 'pain perception' OR
'pain perception'/exp OR 'pain intensity' OR disability OR functionality OR 'disability
evaluation'/exp OR 'treatment outcome'/exp OR 'therapy effect') AND ([controlled clinical
trial]/lim OR [randomized controlled trial]/lim) AND ([article]/lim OR [article in press]/lim)
AND [humans]/lim AND [embase]/lim
Cochrane Central Register of Controlled Trials (CENTRAL) search strategy

((("chronic pain" OR [mh "Chronic Pain"] OR "long-lasting pain" OR "persisting pain" OR "long-
term pain") AND (((idiopathic OR aspecific OR non-specific OR non-traumatic) AND ("neck
pain" OR neckache OR "cervical pain" OR "Cervical disorder*" OR [mh "Neck Pain"])) OR
fibromyalgia OR fibrositis OR [mh "myofascial pain syndromes"] OR [mh Fibromyalgia] OR
whiplash OR "whiplash injuries" OR [mh "Whiplash Injuries"] OR "whiplash associated
disorders") AND (exercise OR "exercise therap*" OR [mh "Exercise Movement Techniques"] OR
[mh "Exercise Therapy"] OR [mh Exercise] OR [mh Rehabilitation] OR Rehabilitation OR [mh
Hydrotherapy] OR "Water therap*" OR "Physical Fitness" OR "Physical Endurance" OR
Pliability OR [mh "Tai Ji"] OR Movement OR rehab OR Run OR Ran OR Running OR Jog OR
Jogging OR Swim* OR swimming OR Walk* OR walking OR cycle* OR cycling OR bicycl* OR
"Motor Activit*" OR Training* OR Stretch* OR Strengthening OR strength* OR "Motion
therap*" OR gymnast* OR isometric* OR isotonic* OR isokinetic* OR aerobic* OR
physiotherap* OR kinesiotherap* OR Stabili* OR segment* OR "motor control" OR ((McKenzie
OR Alexander OR William OR Feldenkrais) adj (technique OR method OR methods)) OR Yoga
OR Pilates OR "Aerobic exercise*" OR Endurance OR "Therapeutic exercise*") AND (pain OR
[mh "Neck Pain"] OR "pain perception" OR [mh "Pain Perception"] OR "pain intensity" OR

disability OR functionality OR [mh "Disability Evaluation"] OR [mh "treatment outcome"] OR
Accepted Article
"therapy effect")))
Limits:
Trials; Search word variations
Cumulative Index to Nursing and Allied Health Literature (CINAHL) search strategy
((("chronic pain" OR (MH "Chronic Pain+") OR "long-lasting pain" OR "persisting pain" OR
"long-term pain") AND (((idiopathic OR aspecific OR non-specific OR non-traumatic) AND
("neck pain" OR neckache OR "cervical pain" OR "Cervical disorder*" OR (MH "Neck Pain+")))
OR fibromyalgia OR fibrositis OR (MH "myofascial pain syndromes+") OR (MH
"Fibromyalgia+") OR whiplash OR "whiplash injuries" OR (MH "Whiplash Injuries+") OR
"whiplash associated disorders") AND (exercise OR "exercise therap*" OR (MH "Exercise
Movement Techniques+") OR (MH "Exercise Therapy+") OR (MH "Exercise+") OR (MH
"Rehabilitation+") OR Rehabilitation OR (MH "Hydrotherapy+") OR "Water therap*" OR
"Physical Fitness" OR "Physical Endurance" OR Pliability OR (MH "Tai Ji+") OR Movement OR
rehab OR Run OR Ran OR Running OR Jog OR Jogging OR Swim* OR swimming OR Walk*
OR walking OR cycle* OR cycling OR bicycl* OR "Motor Activit*" OR Training* OR Stretch*
OR Strengthening OR strength* OR "Motion therap*" OR gymnast* OR isometric* OR isotonic*
OR isokinetic* OR aerobic* OR physiotherap* OR kinesiotherap* OR Stabili* OR segment* OR
"motor control" OR ((McKenzie OR Alexander OR William OR Feldenkrais) adj (technique OR
method OR methods)) OR Yoga OR Pilates OR "Aerobic exercise*" OR Endurance OR
"Therapeutic exercise*") AND (pain OR (MH "Neck Pain+") OR "pain perception" OR (MH
"Pain Perception+") OR "pain intensity" OR disability OR functionality OR (MH "Disability
Evaluation+") OR (MH "treatment outcome+") OR "therapy effect")))
Limits:
Exclude MEDLINE records; Human; Randomized Controlled Trials
Search modes - SmartText Searching
Physiotherapy Evidence Database (PEDro) search strategy

exercise AND fibromyalgia
exercise AND neck pain
exercise AND whiplash
Limits: Method: clinical trial

Table 1. Summary of the exercise prescriptions recommended by this review
Accepted Article FIBROMYALGIA
Type of exercise Global exercises were more researched and presented better
results, such as:
Aerobic exercises;
Muscle strengthening;
Combined exercises (balance + motor control exercises OR
relaxation + stretching exercises OR aerobic + strengthening
+ stretching exercises);
Tai Chi.
No difference between land and pool-based aerobic exercise.
Supervision Supervised
Duration of the session 50 to 60 minutes
Weekly frequency 2 to 3 times a week
Duration of treatment 13 to 24 weeks
Intensity
Aerobic exercises 40% to 80% HRmax; or
Perceived exertion between 9 to 15 on RPE
Muscle strengthening 45 to 50% of 1RM
Muscle stretching Until moderate discomfort
CHRONIC WHIPLASH-ASSOCIATED DISORDER (CWAD)
Type of exercise The most recommended exercises were:
Body awareness exercises;
Combined exercises (aerobic + strengthening + coordination
exercises OR muscle strength + muscle endurance exercises
with or without sling exercises).
The addition of sling exercises to the combination of muscle
strength + muscle endurance exercises did not make any
difference.
This recommendation is based on only two studies.
Duration of the session 90 minutes
Weekly frequency Twice a week
Intensity No information
CHRONIC IDIOPATHIC NECK PAIN (CINP)

Type of exercise Specific exercises were more researched and presented better
Accepted Article results, such as:
Motor control;
Muscle strengthening (muscle strength + muscle endurance);
Combined exercises (aerobic + active range of motion of the
cervical OR shoulder/thoracic + muscle endurance + muscle
strength + stretching exercises OR proprioceptive +
isometric + dynamic mobilization + stretching +
strengthening of the neck + core exercises);
Active range of motion exercises;
Yoga;
Proprioceptive exercises.
No difference between performing muscle strengthening
exercise with focus on muscle strength or muscle endurance.
Duration of the session 30 to 60 minutes
Weekly frequency 2 to 3 times a week
Intensity
Aerobic exercises 50% to 75% of VO2max
Muscle strengthening 20 to 80% of MVC maximum voluntary contraction/or MIC; or
15 to 8 RMs
Motor control Isometric contractions of 10 sec using an inflated pressure
biofeedback device of 20 to 33 mmHg
Abbreviations - HRmax: Maximal heart rate; RPE: Rated perceived exertion scale; RM: Repetition
maximum; MVC: Maximum voluntary contraction; MIC: Maximal isometric contraction; VO2max:
Maximal oxygen uptake; sec: Seconds.

ejp_1666_f1.docx
Accepted Article
PUBMED
N= 554
EMBASE
N= 147
CENTRAL
N= 267
CINAHL
N= 9
PEDro
N= 433
Manual search
N= 3
Records identified through database search

N = 1413
Duplicate records
N= 351
Records screened Records excluded

N = 1062 (N= 971):
Population (N=209)
Intervention (N=474)
Study design (N=272)
Outcome (N=13)
Language (N=3)
Full-text articles screened
N = 91
Full-text articles
excluded (N= 41):
Population (N=4)
Intervention (N=31)
Study design (N=3)
Studies included in the descriptive synthesis Outcome (N=2)
N = 50 Insufficient data for
inclusion (N=1)
Studies included in the quantitative synthesis

(meta-analysis)
N = 24

ejp_1666_f2.pdf
Accepted Article

ejp_1666_f3.pdf
Accepted Article

ejp_1666_f4.pdf
Accepted Article
(a) Forest plot - Aerobic exercise versus Muscle strengthening for pain in short-term
(b) Forest plot - Aerobic exercise versus Muscle stretching for pain in short-term
(c) Forest plot - Land-based aerobic exercise versus Pool-based aerobic exercise for pain in short-term
(d) Forest plot - Muscle strengthening versus Muscle stretching for pain in short-term
(e) Forest plot - Supervised versus Unsupervised exercise for pain in short-term
(f) Forest plot - High intensity aerobic exercise versus Low intensity aerobic exercise for pain in short-term

ejp_1666_f5.pdf
Accepted Article
(a) Forest plot - Motor control versus Nonspecific strengthening exercise for pain in short-term
(b) Forest plot - Mind-body therapies versus Combined exercise for pain in short-term

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Accepted Article

Article type : Review Article

Running title: Prescription of exercises for chronic pain

Significance: The pain mechanism must be considered to optimize exercise prescription in

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Risk of bias assessment

Quality of the evidence

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Data extraction and analysis

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General characteristics of the studies

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Exercise prescription parameters for fibromyalgia

Aerobic exercise versus Muscle stretching

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Land-based aerobic exercise versus Water-based aerobic exercise

Muscle strengthening versus Muscle stretching

Intensity of the exercise

Adverse effects of exercise

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Exercise prescription parameters for chronic whiplash-associated disorders

Combined exercise versus other Combined exercise

Duration of the session

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Weekly treatment frequency

Intensity of the exercise

Adverse effects of exercise

Exercise prescription parameters for chronic idiopathic neck pain

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Mind-body exercises (Qigong and Tai Chi) versus Combined exercise

Adverse effects of exercise

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Strengths and weaknesses

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Implications for practice

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