电针镇痛累积效应和临床疗效关系密切，但其机制尚不清楚。AMPK是治疗疼痛的有效靶点，和参与电针镇痛的内源性镇痛物质关系密切。前期工作表明，多次电针对炎症痛发挥镇痛累积效应的同时，显著活化外周和脊髓的AMPK，而单次电针无此作用。在此基础上，我们将采用痛行为学、分子生物学、条件性基因敲除、光遗传学、荧光双标免疫组化等技术，首先研究电针发挥镇痛累积效应时AMPK激活的时空特征和穴位特异性，其次阐明多次电针持续促进内源性镇痛物质如阿片、大麻、腺苷的合成和释放，激活AMPK这一共同镇痛分子的上游神经生物学机制，最后阐明AMPK继而在外周促进内源性镇痛物质合成和释放（扶正），抑制致炎细胞因子合成和释放（祛邪），在中枢抑制脊髓神经元的敏感化（消除疼痛记忆），介导电针镇痛的累积效应的下游神经生物学机制。本项目旨在阐明AMPK参与电针镇痛累积效应的神经生物学机制，为电针治疗各种疼痛性疾病提供科学依据。

The cumulative effect of electroacupuncture（EA）analgesia is closely related to clinical efficacy, but its mechanism is still unclear. Adenosine monophosphate-activated protein kinase (AMPK) is an effective target for pain treatment and is closely related to endogenous analgesics known to be involved in EA analgesia. Our preliminary data suggested that multiple EA showed analgesic cumulative effects on inflammatory pain, and significantly activated AMPK in the peripheral and spinal cord. Based on these findings, we will use techniques such as pain behavior, molecular biology, conditional gene knockout, optogenetics and Fluorescence double - labeled immunohistochemical method to study AMPK as the link to EA analgesia. At first, we determine the spatial-temporal characters and acupoint specificity of activated AMPK mediating cumulative effect of EA analgesia. Secondly, we investigate the upstream neurobiological mechanism of EA activating AMPK. Multiple EA treatment persistently promote the synthesis and release of endogenous analgesic substances such as opioids, cannabinoid and adenosine, which may activate the common analgesic molecule AMPK. At last, we clarify the downstream neurobiologcal mechanisms of cumulative effect of EA analgesia mediated by AMPK. We wonder whether activated AMPK could promote the synthesis and release of endogenous analgesic substances (strengthening vital qi) in periphery and inhibit the synthesis and release of proinflammatory cytokines (eliminating pathogen) and sensitization of neuron (eliminating pain memory) in spinal cord. The aim of this proposal is to investigate the neurobiological mechanisms of cumulative effect of EA analgesia mediated by AMPK. Findings from the proposed studies could provide scientific basis for clinical application of EA treating various painful illness.