Neural Mechanisms Underlying Acupuncture Analgesia

描述（由申请人提供）：针灸是一种有吸引力的疼痛控制技术，因为它可以通过微创手段唤起内源性镇痛机制。然而，针灸的机制还没有得到很好的理解，阻碍这种理解的主要问题之一是缺乏适当的实验模型。本研究建立了一种电针镇痛的踝关节扭伤模型。该模型给出了踝关节持续性疼痛的可重复和可量化的指数，初步数据显示，在该模型中，在远程部位针刺产生持久的镇痛作用。这通过以下发现表明：EA导致踝关节扭伤的后肢负重恢复约40%。这种可重复性和对针灸的敏感性将使人们能够比以前更详细地追求这种现象的神经机制。提出了四个具体目标。目的1：利用行为学和电生理技术研究电针镇痛传入神经纤维的来源和纤维大小。目的二是用药理学和神经化学方法检测电针是否通过下行系统诱导脊髓NE释放。目的3：研究踝关节扭伤是否引起脊髓中枢敏感化和外周伤害感受器敏感化，电针是否降低中枢敏感化水平。目的4是验证电针激活的中枢神经系统关键结构是否是前顶盖前核（APtN），它投射到脑干去甲肾上腺素能细胞群，在脊髓中释放NE。本研究的成功完成将揭示踝关节扭伤疼痛的针灸镇痛机制。这些知识可以应用于其他形式的疼痛条件下的针刺镇痛，从而获得洞察力，建立一个最有效的手段，利用这种内源性镇痛系统。了解这些机制是必要的，如果针灸是进入主流的医学治疗。

DESCRIPTION (provided by applicant): Acupuncture is appealing pain control technique in that it can evoke endogenous analgesic mechanisms by minimally invasive means. The mechanisms of acupuncture are not well understood, however, and one of the major problems impeding this understanding is a lack of proper experimental models. The present proposal describes a model of electroacupuncture (EA)- induced analgesia in ankle sprain pain. This model gives a repeatable and quantifiable index of persistent pain in the ankle joint and the preliminary data show that acupuncture at a remote site produces long-lasting analgesia in this model. This is shown by the finding the EA results in about 40% recovery of weight bearing by the hind limb with ankle sprain. This reproducibility and susceptibility to acupuncture will allow one to pursue the neural mechanisms of this phenomenon in considerably greater detail than has previously been possible. Four specific aims are proposed. Aim 1 is to investigate the origin and the fiber size group of afferent nerve fibers mediating EA analgesia using behavioral testing and electrophysiological techniques. Aim 2 is to test if EA induces NE release in the spinal cord by a descending system using pharmacological and neurochemical methods. Aim 3 is to test if ankle sprain induces central sensitization in the spinal cord as well as sensitization of peripheral nociceptors and EA reduces the level of central sensitization. Aim 4 is to test if the key CNS structures activated by EA is the anterior pretectal nucleus (APtN), which projects to brainstem noradrenergic cell groups to release NE in the spinal cord. Successful completion of this proposal will unveil important mechanisms underlying acupuncture analgesia in ankle sprain pain. This knowledge can then be applied to acupuncture analgesia in other forms of painful conditions, thereby gaining the insight to establish a maximally effective means of utilizing this endogenous analgesic system. An understanding of these mechanisms is necessary if acupuncture is to move into the mainstream of medical therapy.