Abstract
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.
Highlights
Neuropathic pain (NP) is an important public health issue, with a prevalence ranging from 3.3 to 8.2% (1)
The results showed exercise increased mechanical withdrawal threshold at 1 week (n = 212, Mean differences (MDs) = 0.91, 95% confidence intervals (CIs) 0.11–1.71, I2 = 87%), 2 weeks (n = 202, MD = 3.11, 95% CI 1.56–4.66, I2 = 96%), 3 weeks (n = 200, MD = 3.48, 95% CI 2.70–4.26, I2 = 82%), 4 weeks (n = 182, MD = 4.16, 95% CI 2.53–5.79, I2 = 96%), and 5 weeks (n = 138, MD = 5.58, 95% CI 3.44–7.73, I2 = 97%) (Figure 2) The results of subgroup analyses are described in Table 3 and revealed that the effects varied across different NP models and exercise programs
Eight studies (12, 14–17, 19, 20, 23) with 140 rats were included in the meta-analysis (Figure 3), and the results found that the thermal withdrawal latency was increased in the exercised group compared with the control groups at 1 week (n = 140, MD = 2.48, 95% CI 0.59–4.38, I2 = 93%), 2 weeks (n = 140, MD = 3.57, 95% CI 2.10–5.05, I2 = 87%), 3 weeks (n = 140, MD = 3.92, 95% CI 2.82–5.03, I2 = 69%), and 4 weeks (n = 120, MD = 2.84, 95% CI 1.29–4.39, I2 = 86%)
Summary
Neuropathic pain (NP) is an important public health issue, with a prevalence ranging from 3.3 to 8.2% (1). In 2008, NP has been redefined as pain caused by a lesion or disease of the somatosensory system by the Assessment Committee of the NP Special Interest Group (NeuPSIG) (3). Various causes for NP have been observed, including trauma, infection (e.g., herpes zoster virus), metabolic abnormality (e.g., diabetic neuropathy), neurotoxin (e.g., chemotherapy drug), and tumor infiltration. Patients with conditions frequently experience daily pain that greatly reduces their health-related quality of life. There is accumulating evidence showing that exercise therapy may play an active role in peripheral neuropathic pain (NP). There have been no meta-analysis to investigate the effects of exercise on NP induced by peripheral nerve injury in rat models
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