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

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.

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

“…In general, aerobic exercise protocols reduce exaggerated responses (i.e., hypersensitivities) to these tests. In fact, recent metaanalyses concluded exercise training reduced nociceptive responses to mechanical and thermal tests compared to no exercise controls in animal models of peripheral nerve injury (i.e., SNI and DPN) [56] and SCI [57].…”

Metformin: A Prospective Alternative for the Treatment of Chronic Pain

“…Treatment with mirogabalin (3–10 mg/kg) relieves nerve injury-related anxiety-type behaviors and tactile allodynia ( Murasawa et al., 2020 ), suggesting that reduction of neuropathic pain could lead to a reduction of the comorbidities. Pre-clinical studies have suggested that forced physical exercise decreases neuropathic pain in rodents ( Kuphal et al., 2007 ; Chen et al., 2012 ; Groover et al., 2013 ; Guo et al., 2019 ). Exercise improves physical function and fibromyalgia symptoms ( Schachter et al., 2003 ).…”

Physiotherapy for people with painful peripheral neuropathies: a narrative review of its efficacy and safety

“…The 2 main types of exercises examined in the preclinical literature are aerobic (eg, running and swimming) and passive neurodynamic treatments. There is convincing evidence that aerobic exercise not only reverses established neuropathic pain, 31 but also prevents its development. 29 Aerobic exercise seems more beneficial than resistance exercise for motor nerve regeneration and functional recovery, although this remains to be confirmed for sensory measures.…”

“… 35 The beneficial effects of aerobic exercises have been attributed to a regulation of inflammatory cytokines, neurotrophins, neurotransmitters, endogenous opioids, ion channel function, and descending inhibition as well as axonal and myelin regeneration capacity. 31 , 40 Intriguingly, the neuroprotective benefits of aerobic exercise are influenced less by the type of exercise (eg, swimming vs running) than by other variables. For example, exercise dosage affects neuroprotection: it seems that low-to-moderate intensity exercise is neuroprotective but moderate-to-high intensity exercise can be neurotoxic.…”