Neural Mechanisms Underlying Acupuncture Analgesia

描述（由申请人提供）：针灸是一种很有吸引力的疼痛控制技术，因为它可以通过微创的方式唤起内源性镇痛机制。然而，针灸的机制还没有被很好地理解，阻碍这种理解的主要问题之一是缺乏适当的实验模型。本文描述了一种电针（EA）诱导的踝关节扭伤镇痛模型。该模型给出了踝关节持续疼痛的可重复和可量化的指标，初步数据表明，在该模型中，远距离针灸可以产生持久的镇痛。研究结果表明，在踝关节扭伤的情况下，EA可以使后肢的负重恢复40%。这种对针灸的可重复性和易感性将使人们能够比以前更详细地研究这种现象的神经机制。提出了四个具体目标。目的1：应用行为学测试和电生理技术探讨介导EA镇痛的传入神经纤维的来源和纤维大小群。目的2是使用药理学和神经化学方法测试EA是否通过下行系统诱导NE在脊髓中的释放。目的3是测试踝关节扭伤是否会引起脊髓的中枢致敏以及周围伤害感受器的致敏，EA是否会降低中枢致敏水平。目的4是测试EA激活的关键中枢神经系统结构是否为前前额核（APtN）， APtN投射到脑干去肾上腺素能细胞群，释放脊髓内的NE。这项研究的成功完成将揭示针刺镇痛治疗踝关节扭伤的重要机制。这些知识可以应用于针刺镇痛在其他形式的疼痛条件，从而获得洞察力，建立一个最大有效的手段利用这一内源性镇痛系统。如果针灸要进入医学治疗的主流，对这些机制的理解是必要的。

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.