Effect of Type and Dose of Exercise on Neuropathic Pain After Experimental Sciatic Nerve Injury: A Preclinical Systematic Review and Meta-Analysis

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.