穴位是决定针刺治疗疾病效果的关键因素之一，穴位敏化是疾病状态下穴位从“静息态”转向“激活态”的表现。申请人所在团队研究发现神经中枢可以调节穴位敏化，但中枢神经网络结构尚不明确，其关键核团的调控作用亦不明晰。本课题基于穴位敏化的外在表现，提出“中枢神经网络是调控穴位敏化的基础，下丘脑orexin神经元-RVM-脊髓背角通路是调控穴位‘开-合’的关键”，据此拟综合运用影像学、行为学、神经示踪、DREADD及tettag-DREADD等先进神经科学技术手段，以膝骨关节炎为代表的疾病模型，探索中枢神经调控网络的构成和层级关系，以及下丘脑orexin神经元-RVM对穴位敏化的调节机制，明确敏化穴位在针刺效应中的关键作用。本课题有望从现代解剖学与神经生物学角度诠释穴位敏化的调控机制，丰富中医针刺理论的科学内涵，并为针刺选穴及保障临床合理应用奠定科学基础。

Acupoints are one of the key factors determining the therapeutic effect of acupuncture. Acupoint sensitization refers to the transition of acupoints from the “resting state” to the “activated state” under diseased conditions. Previous studies of our group found that central sensitization is one of the key mechanisms of acupoint sensitization, but the composition of this central network and the regulatory effect of key nuclei need further exploration. The present study hypothesized that “the central network is the physiological basis of regulation of acupoint sensitization, and orexin neurons of the hypothalamus-RVM-dorsal horn of the spinal cord is one of the essential pathways for regulating the switch between “on” and “off” of acupoints. This will be tested in a chronic knee osteoarthritis mouse model using imaging, behavioural, neurotracing, and other emerging neuroscience techniques such as DREADD and tettag-DREADD. The ultimate goal is to describe the composition of the central network and the connections of orexin neurons and RVM, and to elucidate the mechanism with which orexin neurons of the hypothalamus and RVM regulate acupoint sensitization, and to confirm the pivotal role of sensitized acupoints in determining the therapeutic effect of acupuncture. Results from this study will not only help to explain the biological mechanism of acupoint sensitization from a point view of modern neuroanatomy and neurobiology, but also enrich the theory of Traditional Chinese Medicine and lay the scientific foundation for acupoint selection as well as its appropriate application.