推拿调控PAG-RVM-DH通路下行抑制信号对膝骨关节炎镇痛作用机制研究

疼痛是膝骨关节炎（KOA）临床亟待解决的问题。最新指南指出在KOA阶梯化治疗中药物和手术有严格适应症，推拿作为第一阶梯疗法，镇痛作用肯定，在KOA各临床分期均可应用。疼痛下行抑制系统在KOA疼痛中发挥着重要作用，其中导水管周围灰质(PAG)-延髓头端腹内侧区(RVM)-脊髓背角(DH)通路起关键作用。我们前期多模态MRI推拿镇痛研究发现RVM脑功能活动增强，动物实验发现PAG-RVM-DH通路参与推拿镇痛调控，但推拿如何调控该通路对KOA发挥镇痛效应尚不明确。因此，本项目提出“推拿激活疼痛下行抑制系统PAG-RVM-DH通路改善膝周‘筋痹’疼痛”假说，拟开展临床fMRI成像研究和动物脑区毁损实验研究：①基于fMRI揭示推拿调控PAG-RVM通路对KOA患者镇痛作用研究；②推拿调控PAG-RVM-DH通路对KOA模型大鼠镇痛作用机制研究。为KOA临床镇痛方案的优化提供现代科学依据。

Pain is an urgent problem in the clinical treatment of knee osteoarthritis (KOA). According to the latest guideline, there are strict indications for medication and surgery in the step-by-step treatment of KOA. As the first step therapy, Tuina has definite analgesic effect and can be applied in all clinical stages of KOA. The descending inhibition system of pain plays an important role in KOA pain, in which the periaqueductal gray (PAG) to rostral ventromedial medulla (RVM) to dorsal horn of spinal cord (DH) pathway plays a key role. In our previous multimodal MRI Tuina analgesia study, we found that RVM brain function activity was enhanced, and animal experiments found that PAG-RVM-DH pathway was involved in the regulation of Tuina analgesia. However, how Tuina regulates this pathway to exert analgesic effect on KOA is not clear. Therefore, this project puts forward the hypothesis that Tuina can activate the PAG-RVM-DH pathway of descending inhibition system of pain to improve the pain of Jinbi around the knee, and intends to carry out clinical fMRI imaging research and animal brain damage experiment: ①Analgesic effect of Tuina for KOA patients via regulating PAG-RVM pathway detected by fMRI; ②Analgesic mechanism of Tuina for KOA model rats via regulating PAG-RVM-DH pathway. Objective to provide modern scientific basis for the optimization of KOA clinical analgesia.