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

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. 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. 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. 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.