CB2R负性调控MAPK信号通路——从脊髓敏化角度研究电针治疗骨性关节炎慢性疼痛的康复新机制

骨性关节炎(OA)慢性疼痛是导致50岁以上人群劳动力丧失的重要原因，电针治疗OA慢性疼痛疗效确切，但相关机制仍不明确。研究发现，脊髓敏化参与OA疼痛慢性化进程，大麻素受体2(CB2R)对脊髓敏化具有调控作用。本课题拟从“脊髓敏化参与OA慢性疼痛”切入，研究电针治疗OA慢性疼痛的作用机制，提出“电针通过CB2R负性调控MAPK信号通路，进而抑制脊髓敏化发挥OA镇痛效应”的假说。研究将以MIA诱导的膝OA慢性疼痛大鼠为研究对象，采用“阳陵泉、内膝眼”穴电针作为干预手段，利用免疫荧光、ELISA、实时荧光定量PCR和Western blot等现代检测技术，从不同层次和不同时间观察电针对OA脊髓敏化的调控作用及其与脊髓CB2R活性和MAPK信号通路的相关性。有望从脊髓敏化角度阐明电针抑制OA慢性疼痛的作用机制，为电针治疗OA慢性疼痛提供新的研究靶点，为临床应用电针治疗OA慢性疼痛提供新的科学依据。

Chronic pain of osteoarthritis (OA) is an important reason for the loss of labor force in people over 50 years of age. The effect of electroacupuncture on OA chronic pain is reliable, but the mechanism remains unclear. Previous studies show that central sensitization of spinal level may contribute to the chronic process of OA pain, and cannabinoid receptor 2(CB2R) plays a regulatory role in spinal sensitization. Taking the viewpoint that spinal sensitization participates in the OA chronic pain as an entry point, this research focuses on  the mechanism of electroacupuncture on chronic pain in OA, and the hypothesis is put forward that the effects of electroacupuncture in inhibiting OA chronic pain is relevant to the fact that electroacupuncture could negatively regulate MAPK signaling pathway through CB2R, and thereby inhibit spinal sensitization. In this research, MIA-induced rat model of OA joint pain is to be used as the research object, electroacupuncture of Nei xi yan and Yanglingquan points is to be selected as interventions, and that the regulating effects of electroacupuncture on spinal sensitization of OA chronic pain and its correlation with the activity of spinal cord CB2R and MAPK signaling pathway are to be observed at different level and different time through the methods of immunofluorescence, ELISA, real time quantitative PCR as well as Western blot. It is expected to elucidate the mechanism of electroacupuncture on inhibition of OA chronic pain from the aspect of spinal sensitization，and therefore to provide a new target for the research of electroacupuncture in treatment of chronic pain of OA and provide new scientific basis for clinical application of electroacupuncture on chronic pain of OA.