Meta-Analysis of the Effect of Exercise on Neuropathic Pain Induced by Peripheral Nerve Injury in Rat Models

Background: There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP). However, there have been no meta-analysis to investigate the effects of exercise on NP induced by peripheral nerve injury in rat models. Methods: PubMed, EMBASE, and Web of Science were searched from inception to January 2019. A random-effect model was implemented to provide effect estimates for pain-related behavioral test outcome. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: Fourteen studies were included. For the mechanical withdrawal threshold, rats in the exercised group exhibited significantly higher thresholds than those in the control group, with a MD of 0.91 (95% CI 0.11–1.71), 3.11 (95% CI 1.56–4.66), 3.48 (95% CI 2.70–4.26), 4.16 (95% CI 2.53–5.79), and 5.58 (95% CI 3.44–7.73) at 1, 2, 3, 4, and 5 weeks, respectively. Additionally, thermal withdrawal latency increased in the exercised group compared with the control group, with a MD of 2.48 (95% CI 0.59–4.38), 3.57 (95% CI 2.10–5.05), 3.92 (95% CI 2.82–5.03), and 2.84 (95% CI 1.29–4.39) at 1, 2, 3, and 4 weeks, respectively. Subgroup analyses were performed for pain models, exercise start point, exercise forms, and duration, which decreased heterogeneity to some extent. Conclusion: This meta-analysis indicated that exercise provoked an increase in mechanical withdrawal threshold and thermal withdrawal latency in animal NP models. Exercise therapy may be a promising non-pharmacologic therapy to prevent the development of NP. Further, preclinical studies focused on improving experiment design and reporting are still needed.