Manual Massage Therapy for Neuropathic Pain: Clinical Evidence and Mechanistic Insights

Neuropathic pain (NP) is a complex chronic pain condition arising from a lesion or disease of the somatosensory nervous system, presenting significant clinical challenges with limited therapeutic efficacy from conventional pharmacological interventions. Massage, as a specific form of manual therapy, is a pivotal therapeutic modality in traditional Chinese medicine (TCM) and has been increasingly adopted for the management of NP due to its noninvasive nature and favorable safety profile. Recent advances in clinical and basic research indicate that massage not only effectively mitigates pain symptoms and ameliorates functional impairment and emotional disturbances but also exerts analgesic effects by modulating inflammatory responses, regulating ion channel function, controlling synaptic plasticity at the spinal level, and inducing brain functional remodeling. This review synthesizes and critically evaluates current evidence regarding the application of massage for NP, integrating findings from both animal studies and clinical trials. It systematically analyzes potential molecular and cellular mechanisms, including the HMGB1/NF-κB pathway, mechanosensitive Piezo channels, the astrocytic NDRG2/GLT-1 pathway, and the default mode network (DMN). By critically synthesizing the underlying mechanisms of massage, this review aims to provide a theoretical basis for clinical promotion and mechanistic research, thereby advancing the development of comprehensive, potentially disease-modifying therapeutic strategies for NP.