Table_2_Meta-Analysis of the Effect of Exercise on Neuropathic Pain Induced by Peripheral Nerve Injury in Rat Models.DOCX

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.

背景：现有越来越多的证据表明，运动疗法可能在周围神经性疼痛（peripheral neuropathic pain, NP）的发生发展中发挥积极作用。然而，目前尚无荟萃分析（meta-analysis）探讨运动对大鼠模型中周围神经损伤诱导的周围神经性疼痛的干预效应。
方法：检索PubMed、EMBASE及Web of Science数据库，检索时限为各数据库建库至2019年1月。采用随机效应模型（random-effect model）对疼痛相关行为学测试的结局指标进行效应量估计，计算均数差（mean differences, MDs）及其95%置信区间（confidence intervals, CIs）。
结果：共纳入14项相关研究。针对机械撤足阈值，运动组大鼠在造模后1、2、3、4、5周的阈值均显著高于对照组，对应的均数差分别为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）及5.58（95% CI：3.44~7.73）。此外，运动组大鼠的热撤足潜伏期较对照组显著升高，造模后1、2、3、4周对应的均数差分别为2.48（95% CI：0.59~4.38）、3.57（95% CI：2.10~5.05）、3.92（95% CI：2.82~5.03）及2.84（95% CI：1.29~4.39）。本研究针对疼痛模型类型、运动起始时机、运动形式及运动时长开展亚组分析，一定程度上降低了研究异质性。
结论：本项荟萃分析结果显示，运动可显著提升大鼠周围神经性疼痛模型的机械撤足阈值与热撤足潜伏期。运动疗法或为一种极具应用前景的非药物治疗手段，可用于预防周围神经性疼痛的发生与进展。此外，仍需开展聚焦于优化实验设计与报告规范的临床前研究。