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Original research
Central neurobiological effects of physical exercise in individuals with chronic musculoskeletal pain: a systematic review
  1. Rutger M J de Zoete1,2,
  2. Kenneth Chen1,3,
  3. Michele Sterling1
  1. 1RECOVER Injury Research Centre, NHMRC Centre of Research Excellence in Recovery Following Road Traffic Injuries, The University of Queensland, Herston, Queensland, Australia
  2. 2School of Allied Health Science and Practice, The University of Adelaide, Adelaide, South Australia, Australia
  3. 3Geriatric Education and Research Institute, Singapore
  1. Correspondence to Dr Rutger M J de Zoete; rutger.dezoete{at}


Objective Primary objectives: to investigate the central neurobiological effects (using MRI) of physical exercise in individuals with chronic pain. Secondary objectives: (1) to investigate the associations between central changes and clinical outcomes and (2) to investigate whether different types and dosages of physical exercise exert different central changes.

Design Systematic review searching four electronic databases up to September 2018: AMED, CINAHL, Embase and MEDLINE. Two reviewers independently assessed the methodological quality of included studies using the Cochrane Collaboration’s Risk of Bias in Non-Randomised Studies-I tool. A standardised extraction table was used for data extraction, which was performed by two reviewers.

Interventions Studies reporting any physical exercise intervention in any chronic musculoskeletal pain condition were included. Eligibility of 4011 records was screened independently by two reviewers, and four studies were included in the review.

Primary and secondary outcome measures Primary outcome: any brain outcome assessed with any MR technique. Secondary outcomes: any self-reported clinical outcomes, and type and dosage of the exercise intervention.

Results All four studies had high risk of bias. There was heterogeneity between the brain areas studied and the types of exercise interventions delivered. All studies reported functional MRI changes in various brain areas following an exercise intervention. Insufficient data were available to conduct a meta-analysis or to answer the secondary aims.

Conclusions Only a limited number of studies were available and all were at high risk of bias. None of the studies was randomised or included blinded assessment. Exercise may exert effects on brain neurobiology in people with chronic pain. Due to the high risk of bias, future studies should use a randomised study design. Investigation of morphological brain changes could be included.

PROSPERO registration number CRD42018108179.

  • neuroradiology
  • musculoskeletal disorders
  • pain management
  • magnetic resonance imaging
  • rehabilitation medicine

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  • Contributors RMJdZ conceived the content, wrote the paper and approved the final version. KC contributed and approved the final version of the paper. MS conceived the design of the paper and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was not required as data from published studies was used.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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