Abstract: BACKGROUND: The peripheral mechanism of Tuina analgesia remains unclear. This study aimed to investigate whether Tuina acupressure alleviates peripheral sensitization and neuropathic pain by regulating the abnormal signal interaction of the “neuron-satellite glial cell” functional unit in the dorsal root ganglion.
OBJECTIVE: To observe the effects of Tuina on pain behavior and neuron-satellite glial cell signal interaction in the dorsal root ganglion of rats with chronic constriction injury of the sciatic nerve, and to explore the molecular mechanism of Tuina in alleviating neuropathic pain by regulating peripheral sensitization.
METHODS: Twenty-four specific pathogen-free grade male Sprague-Dawley rats were randomly divided into blank control, model, and Tuina groups, with eight rats in each group. The latter two groups were established as chronic constriction injury models of the sciatic nerve. The Tuina group received acupressure intervention at the Weizhong acupoint starting from the 4th day post-surgery, once daily at a force of 5 N and a frequency of 120 times/min for 10 minutes each session, for a total of 14 days. Mechanical paw withdrawal threshold was measured using von Frey filaments, and thermal paw withdrawal latency was measured using a thermal pain instrument. Western blot was used to detect the expression of connexin 43, calcium/calmodulin-dependent serine protein kinase, glial fibrillary acidic protein, and pannexin 1 in the dorsal root ganglion. Enzyme-linked immunosorbent assay was used to detect the expression levels of inflammatory factors tumor necrosis factor α and interleukin 1β in the dorsal root ganglion. Hematoxylin-eosin staining was used to observe the pathological morphology of the gastrocnemius muscle.
RESULTS AND CONCLUSION: (1) Compared with the blank control group, the mechanical paw withdrawal threshold and thermal paw withdrawal latency in the model and Tuina groups were significantly decreased on postoperative day 7 (all P < 0.001). On postoperative days 7, 10, 14, and 17, the mechanical paw withdrawal threshold was significantly higher and the thermal paw withdrawal latency was significantly longer in the Tuina group than in the model group (all P < 0.001). (2) The expression levels of connexin 43, calcium/calmodulin-dependent serine protein kinase, glial fibrillary acidic protein, pannexin 1, tumor necrosis factor α, and interleukin 1β in the dorsal root ganglion were significantly higher in the model group than in the blank control group (all P < 0.05), and these indicators were significantly lower in the Tuina group than in the model group (all P < 0.05). (3) Hematoxylin-eosin staining showed irregular shape and disordered nuclear arrangement of the gastrocnemius muscle in the model group, while the muscle fiber morphology was partially restored in the Tuina group. To conclude, these findings indicate that Tuina may improve peripheral sensitization and pain behavior in rats with chronic constriction injury of the sciatic nerve by inhibiting the expression of connexin 43 and pannexin 1 in neurons and satellite glial cells, attenuating signal interaction between neurons and satellite glial cells, reducing the release of pro-inflammatory factors, and decreasing neuronal excitability. This provides a theoretical basis from a molecular biology perspective for the peripheral analgesic mechanism of Tuina.

Key words: Tuina, pain, dorsal root ganglion, satellite glial cells, peripheral sensitization