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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Article info
Publication history
Accepted:
January 12,
2023
Received in revised form:
December 30,
2022
Received:
September 27,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.
