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Attempting to Separate Placebo Effects from Exercise in Chronic Pain: A Systematic Review and Meta-analysis

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A Letter to the Editor to this article was published on 21 December 2021

A Letter to the Editor to this article was published on 21 December 2021

A Correction to this article was published on 19 October 2021

This article has been updated

Abstract

Background

Pain is the most disabling characteristic of musculoskeletal disorders, and while exercise is promoted as an important treatment modality for chronic musculoskeletal conditions, the relative contribution of the specific effects of exercise training, placebo effects and non-specific effects such as natural history are not clear. The aim of this systematic review and meta-analysis was to determine the relative contribution of these factors to better understand the true effect of exercise training for reducing pain in chronic primary musculoskeletal pain conditions.

Design

Systematic review with meta-analysis

Data Sources

MEDLINE, CINAHL, SPORTDiscus, EMBASE and CENTRAL from inception to February 2021. Reference lists of prior systematic reviews.

Eligibility Criteria

Randomised controlled trials of interventions that used exercise training compared to placebo, true control or usual care in adults with chronic primary musculoskeletal pain. The review was registered prospectively with PROSPERO (CRD42019141096).

Results

We identified 79 eligible trials for quantitative analysis. Pairwise meta-analysis showed very low-quality evidence (GRADE criteria) that exercise training was not more effective than placebo (g [95% CI]: 0.94 [− 0.17, 2.06], P = 0.098, I2 = 92.46%, studies: n = 4). Exercise training was more effective than true, no intervention controls (g [95% CI]: 0.99 [0.66, 1.32], P < 0.001, I2 = 92.43%, studies: n = 42), usual care controls (g [95% CI]: 0.64 [0.44, 0.83], P < 0.001, I2 = 76.52%, studies: n = 33), and when all controls combined (g [95% CI]: 0.84 [0.64, 1.04], P < 0.001, I2 = 90.02%, studies: n = 79).

Conclusions

There is very low-quality evidence that exercise training is not more effective than non-exercise placebo treatments in chronic pain. Exercise training and the associated clinical encounter are more effective than true control or standard medical care for reductions in pain for adults with chronic musculoskeletal pain, with very low quality of evidence based on GRADE criteria.

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Authors and Affiliations

  1. Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, Australia

    Clint T. Miller, Patrick J. Owen, Kate Sadler & Daniel L. Belavy

  2. School of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane, Australia

    Christian A. Than

  3. School of Medicine and Public Health, University of Newcastle, Callaghan, Newcastle, Australia

    Jake Ball

  4. Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Turin, Italy

    Alessandro Piedimonte & Fabrizio Benedetti

  5. Medicine and Physiology of Hypoxia, Plateau Rosà, Zermatt, Switzerland

    Fabrizio Benedetti

  6. Department of Applied Health Sciences, Division of Physiotherapy, Hochschule für Gesundheit (University of Applied Sciences), Bochum, Germany

    Daniel L. Belavy

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  1. Clint T. Miller
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  2. Patrick J. Owen
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  8. Daniel L. Belavy
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Corresponding author

Correspondence to Clint T. Miller.

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Funding

No funding was provided for this systematic review.

Conflict of interest

Clint Miller, Patrick Owen, Christian Than, Jake Ball, Kate Sadler, Alessandro Piedimonte, Fabrizio Benedetti and Daniel Belavy declare that they have no conflicts of interest relevant to the content of this review.

Data availability

The data extracted as part of this systematic review and used in subsequent analysis are made available in Table 1 and the Stata code and data are included in Table S2 (OSM).

Author contributions

Systematic review conception: CTM, PJO, DLB, AP. Screening: PJO, JB, CAT, KS. Extraction: JB, CAT, KS. Statistical analyses: PJO. Drafted manuscript: CTM. Edited and approved final manuscript: All.

Additional information

The original article has been updated: Due to Figures update.

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Miller, C.T., Owen, P.J., Than, C.A. et al. Attempting to Separate Placebo Effects from Exercise in Chronic Pain: A Systematic Review and Meta-analysis. Sports Med 52, 789–816 (2022). https://doi.org/10.1007/s40279-021-01526-6

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