Role of Piezo2/P2X7/MG pathway in synaptic plasticity and analgesic effects of massage therapy in cervical spondylotic radiculopathy: A preclinical study in animal models

Objective: This study aimed to investigate the synaptic plasticity of the spinal dorsal horn regulated by the Piezo2/P2X7/MG signaling pathway and elucidate its role in the analgesic effects of massage in Cervical Spondylotic Radiculopathy (CSR), with the goal of identifying potential therapeutic targets for effective treatment. Methods: This experimental animal study included 40 Sprague-Dawley rats (180 ± 20 g), randomly divided into four groups (control, model, sham-operated, and massage; n=10 per group) after a one-week acclimation period. The CSR model was established by spinal canal insertion. Blood and spinal cord tissues were collected post-intervention. Mechanical pain threshold (MPT), 50% paw withdrawal threshold (50% PWT), immunofluorescence, Western blot, and qRT-PCR assays were employed to evaluate synaptic plasticity and pathway expression. Results: The massage group demonstrated significantly higher MPT and 50% PWT values compared to the model group post-intervention (P < 0.05). Downregulation of the Piezo2/P2X7/MG signaling pathway was observed in the massage group, correlating with a reduction in CSR progression, while upregulation in the model group promoted CSR (P < 0.05). Conclusion: The Piezo2/P2X7/MG signaling pathway regulates the synaptic plasticity of the spinal dorsal horn in CSR. These findings suggest that massage therapy can effectively alleviate CSR-associated pain by modulating this pathway, offering a potential noninvasive therapeutic approach.