针灸生物学效应机制不清是影响其进一步发扬光大的主要原因。“穴位敏化”是指从生理状态下的“静息态”到病理状态下的“激活态”的现象。穴位敏化现象是如何出现的？穴位敏化的调节机制是什么？目前尚不清楚。本课题基于穴位敏化的表现特征与我们前期的研究结果，首次提出“穴位敏化是中枢敏化的外在表现，中枢神经系统对感觉信息的调节机制是穴位‘开-合’转化的关键”，并拟综合运用microneurography、表观遗传学、双膜片钳全细胞记录、光遗传学、DREADD等先进的神经科学技术手段，以急性心肌缺血和膝骨关节炎为代表性疾病模型，探索DRG初级感觉传入神经元－脊髓后角前馈抑制回路－中脑延髓下行调节系统对敏化穴位的神经调节机制，并明确敏化穴位在针刺效应中的关键作用。本课题研究结果不仅有助于指导选穴与保证临床疗效，也必将进一步丰富中医理论，推动针刺走向世界，具有重大的科学意义和社会价值。

A major obstruction to further develop and glorify acupuncture therapy is the obscure biological mechanism underlying its effect. Acupoint sensitization is a phenomenon that the state of several acupoints changed from resting to active during the transformation from physiological conditions to pathological condition. However, it is still unknown how acupoint sensitization occurs and what regulatory mechanism is in charge. The current project is based on the characteristics of acupoint sensitization and our previous research results on the regulatory mechanism of allodynia. Here we propose for the first time a hypothesis: acupoint sensitization is the external manifestation of central nerves system (CNS) sensitization. The regulatory mechanism of all types of sensations by the CNS is the key for the transformation of acupoint states “from close to open”. Using cutting edge technologies in neuroscience such as microneurography, epigenetic techniques, paired patch-clamp whole-cell recordings, optogenetics and DREADD, the project is to explore that in two representative disease models - acute myocardial ischemia and chronic knee osteoarthritis, the regulatory mechanism of the “primary sensory neurons in the dorsal root ganglia – a feed-forward inhibitory circuit in the spinal cord dorsal horn – and the midbrain/medulla oblongata descending regulatory pathway” on the phenomenon of acupoint sensitization, which will unveil the key mechanism underlying acupoint sensitization and its essence – CNS sensitization. The results of this project will be of great significance and value to guide acupoint selection and guarantee the effectiveness of acupuncture therapy. It will further enrich TCM theory and promote the international application of acupuncture, which will be of great value for science and society.