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Effect of Type and Dose of Exercise on Neuropathic Pain after Experimental Sciatic Nerve Injury: a Preclinical Systematic Review and Meta-analysis.

  • Luis Matesanz-García
    Affiliations
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

    Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Escuela Internacional de Doctorado, Universidad Rey Juan Carlos, Alcorcón, Spain

    Department of Physiotherapy, Centro Superior de Estudios Universitarios La Salle, Universidad Autónoma de Madrid, Madrid, Spain
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  • Clément Billerot
    Affiliations
    Faculty of biology, Euro-Mediterranean Master in Neurosciences and Biotechnology, Université de Bordeaux, Bordeaux, France
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  • Joel Fundaun
    Affiliations
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
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  • Annina B. Schmid
    Correspondence
    Corresponding author: A. Schmid, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, WestWing Level 6, Oxford, OX39DU, United Kingdom
    Affiliations
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
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Published:January 20, 2023DOI:https://doi.org/10.1016/j.jpain.2023.01.011

      Highlights

      • ‘What is already known:
      • Exercise is recommended in clinical guidelines for focal peripheral neuropathic pain
      • Evidence for its benefit is lacking and the optimal exercise type and dose remain unknown
      • ‘What are the new findings:
      • Preclinical data suggest that exercise reduces peripheral nerve injury-induced hypersensitivity
      • Duration and intensity of exercise does not seem to influence this antinociceptive effect
      • Exercise modulates a range of biomarkers, particularly immune-related and neurotrophic factors

      ABSTRACT

      This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behaviour and biomarkers in preclinical models of focal neuropathic pain.
      We searched MEDLINE, EMBASE, Web of Science, PubMed, SCOPUS, CINAHL and Cochrane library from inception to November 2022 for preclinical studies evaluating the effect of exercise compared to control interventions on neuropathic pain behaviour after experimental sciatic nerve injury. If possible, data were meta-analysed using random effect models with inverse-variance weighting.
      Thirty-seven studies were included and 26 meta-analysed. Risk of bias (SYRCLE tool) remained unclear in most studies and reporting quality (CAMARADES) was variable. Exercise reduced mechanical (SMD 0.53 (95% CI 0.31, 0.74), p= 0.0001, I2=0%, n=364), heat (0.32 (0.07,0.57), p=0.01, I2=0%, n=266) and cold hypersensitivity (0.51 (0.03, 1.0), p=0.04, I2=0%, n=90) compared to control interventions. No relationship was apparent between exercise duration or intensity and antinociception. Exercise modulated biomarkers related to different systems (e.g., immune system, neurotrophins).
      Whereas firm conclusions are prevented by the use of male animals only, variable reporting quality and unclear risk of bias in many studies, our results suggest that aerobic exercise is a promising tool in the management of focal neuropathic pain. Registration PROSPERO CRD42021231286.
      Perspective: This systematic review and meta-analysis demonstrates that aerobic exercise reduces neuropathic pain-related behavior in preclinical models of sciatic nerve injury. This effect is accompanied by changes in biomarkers associated with inflammation and neurotrophins among others. These results could help to develop exercise interventions for patients with neuropathic pain.

      KEYWORDS

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