Peripherally-induced neuropathic pain (pNP) is a kind of NP that is common, frequent, and difficult to treat. Tuina, also known as massage and manual therapy, has been used to treat pain in China for thousands of years. It has been clinically proven to be effective in the treatment of pNP caused by cervical spondylosis, lumbar disc herniation, etc. However, its analgesic mechanism is still not clear and has been the focus of research. In this review, we summarize the existing research progress, so as to provide guidance for clinical and basic studies. The analgesic mechanism of tuina is mainly manifested in suppressing peripheral inflammation by regulating the TLR4 pathway and miRNA, modulating ion channels (such as P2X3 and piezo), inhibiting the activation of glial cells, and adjusting the brain functional alterations. Overall, tuina has an analgesic effect by acting on different levels of targets, and it is an effective therapy for the treatment of pNP. It is necessary to continue to study the mechanism of tuina analgesia.

Objective. To study the effects of the three methods and three-acupoint technique on DRG gene expression in SNI model rats and to elucidate the molecular mechanism of the three methods and three-acupoint technique on promoting recovery in peripheral nerve injury. Methods. 27 male SD rats were randomly divided into three groups: a Sham group, the SNI group, and the Tuina group. The Tuina group was treated with a tuina manipulation simulator to simulate massage on points, controlling for both quality and quantity. Point-pressing, plucking, and kneading methods were administered quantitatively at Yinmen (BL37), Chengshan (BL57), and Yanglingquan (GB34) points on the affected side once a day, beginning 7 days after modeling. Intervention was applied once a day for 10 days, then 1 day of rest, followed by 10 more days of intervention, totally equaling 20 times of intervention. The effect of the three methods and three-point technique on the recovery of injured rats was evaluated using behavior analysis. RNA sequencing (RNA-Seq) analysis of differentially expressed genes in DRGs of the three groups of rats was also performed. GO and KEGG enrichment was analyzed and verified using real-time PCR. Results. RNA-Seq combined with database information showed that the number of differentially expressed genes in DRG was the largest in the Tuina group compared with the SNI group, totaling 226. GO function is enriched in the positive regulation of cell processes, ion binding, protein binding, neuron, response to pressure, response to metal ions, neuron projection, and other biological processes. GO function is also enriched in the Wnt, IL-17, and MAPK signaling pathways in the KEGG database. PCR results were consistent with those of RNA sequencing, suggesting that the results of transcriptome sequencing were reliable. Conclusion. The three methods and three-acupoint technique can promote the recovery of SNI model rats by altering the gene sequence in DRGs.

Tuina, as one of the characteristic external therapies of Traditional Chinese Medicine (TCM), has been used to treat the disease caused by peripheral nerve injury (PNI) for thousands of years. An increasing number of clinical trials and animal experiments have demonstrated that tuina can improve the symptoms and promote the recovery of damaged nerves. This review focuses on the mechanistic studies of tuina in promoting the recovery of PNI, which might provide a neurobiological foundation for the effects of tuina. Although many mechanisms underlying the effects of tuina on nerve repair have been identified, there are still many unknown problems, such as the key substance or way for tuina to work, so further investigation is warranted.

Previous studies have proved and investigated the mechanism of the analgesic effect of tuina treatment on neuropathic pain. The purpose of this study was to analyze changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after 1-time tuina intervention to investigate the immediate analgesic mechanism by tuina. An improvement in nociceptive behavior in minor chronic constriction injury (CCI) rats after 1-time tuina was observed. 1-time tuina was more effective in the amelioration of thermal hyperalgesia, but no changes were found in the ultrastructure of DRG and SDH. Sixty-five differentially expressed genes (DEGs) modulated by tuina were detected in the DRG and 123 DEGs were detected in the SDH. Potential immediate analgesic mechanisms of tuina were analyzed by the Kyoto Encyclopedia of Genes and Genomes. DEGs were enriched in 75 pathways in DRG, and 107 pathways in SDH. The immediate analgesic mechanism of tuina is related to the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.

Objective: The objective of this study is to observe the effects of mild mechanical stimulation on acupuncture points of spinal motor neurons and active substances of sciatic nerve injury in rats, and to explore the morphological basis for the recovery of motor function in rats with sciatic nerve injury, using mild acupuncture. Acupuncture in the local area of injury may cause further damage to the peripheral nerve injury. We believe that mild mechanical stimulation on the surface, using some specific acupuncture points can also have a positive effect on nerve repair. This method, called Chinese tuina, has existed for more than 2,000 years in China. Methods: This study establishes a rat model using sciatic nerve crush injury. Rats received Chinese tuina in accordance with the principle of the three methods and three points, once a day, for 20 days. The rats’ status of hindlimb recovery was detected by a sciatic functional index. The labeled neuronal cell body was used to evaluate the fiber recovery after the rats’ sciatic nerve injury, using a neural tracing technique. Our team studied motor neuronal cell bodies, CGRP-positive cells, and the microglia of damaged sciatic nerves which were stained with fluorescent triple staining, adopting a confocal multi-layer scanning technique, and then the changes in neuronal activity distribution and expression, and changes of time and treatment were described, using the method of morphological description. Results: Sciatic nerve injury decreased the survival rate of motor neurons, affected CGRP-positive cells, and activated microglia in the ventral horn of the spinal cord. Compared with the model group, the survival of spinal ventral horn motor neurons was increased through tuina intervention. The swelling of CGRP-positive cells was alleviated, and the degree of microglia activation was less than that of the model group. Conclusion: This study used visual morphological findings to assess changes in neurons and active substances with time after injury of the peripheral nerve, and demonstrated that peripheral mild acupuncture intervention improved the capacity of neurofibrillary axoplasmic transport, regulated microglia activation, and significantly promoted the recovery of sciatic nerve injury.