BACKGROUND: Neuropathic pain is a chronic pain condition caused by direct damage or functional abnormalities in the somatic sensory nervous system. Its clinical manifestations include spontaneous pain and tactile hypersensitivity, which are difficult to control effectively with traditional drug therapies. The pathogenesis of neuropathic pain involves multiple physiological processes, including neuronal hyperexcitability, glial cell activation, neurotransmitter imbalance, immune responses, and oxidative stress. Existing medications and invasive treatments often carry side effects and exhibit significant limitations in efficacy. Therefore, exploring safe and effective non-pharmacological interventions, particularly exercise-based interventions for improving neuropathic pain, has become a critical research focus in the field of neuropathic pain.
OBJECTIVE: To review advances in understanding the mechanisms of neuropathic pain, analyze the potential and mechanisms of exercise intervention in alleviating neuropathic pain, demonstrate the clinical application prospects of exercise as a non-pharmacological intervention strategy, and highlight key directions for future research.
METHODS: Relevant literature was retrieved from databases including PubMed and CNKI using the keywords of “neuropathic pain, neurogenic pain, post-neuropathic pain, exercise, physical activity, aerobic exercise, strength training, yoga, pathogenesis, inflammation, neurotransmitters, neurotrophic factors, oxidative stress, rehabilitation” in Chinese and “neuropathic pain, nerve injury pain, exercise, physical activity, aerobic exercise, resistance training, yoga, pathogenesis, inflammation, neurotransmitter, neurotrophin, oxidative stress, rehabilitation” in English. A total of 139 studies were ultimately included in the analysis, focusing on the core mechanisms of neuropathic pain. The review specifically examined the mechanisms by which exercise alleviates neuropathic pain through multi-targeted, multi-pathway synergistic effects.
RESULTS AND CONCLUSION: The pathogenesis of neuropathic pain involves neuronal hyperexcitability, glial cell activation, neurotransmitter imbalance, immune-inflammatory responses, and oxidative stress-induced nerve damage. Exercise intervention relieves pain by regulating pathways such as modulating neurotransmitter release, promoting neurotrophic factor expression, suppressing inflammatory responses, and mitigating oxidative stress. Specifically, exercise can upregulate neurotrophic factors such as brain-derived neurotrophic factor and nerve growth factor, while inhibiting the release of pro-inflammatory factors such as tumor necrosis factor, thereby modulating core pathways in neuropathic pain development. Simultaneously, it produces analgesic effects by modulating the endogenous opioid system. However, the specific mechanisms by which different exercise modalities alleviate neuropathic pain require further investigation. Significant challenges remain in designing personalized exercise prescriptions and optimizing exercise parameters. Future research should focus on developing and validating exercise protocols, clarifying synergistic effects of exercise combined with pharmacotherapy, and thereby advancing clinical treatment for neuropathic pain.