Neural Mechanisms Underlying Acupuncture Analgesia

描述(申请人提供)：针灸是一种吸引人的疼痛控制技术，因为它可以通过微创方法唤起内源性止痛机制。然而，针灸的机制还不是很清楚，阻碍这一理解的主要问题之一是缺乏适当的实验模型。本方案描述了一种电针(EA)诱导的踝关节扭伤痛的镇痛模型。这个模型给出了一个可重复和可量化的踝关节持续性疼痛指数，初步数据表明，在这个模型中，偏远部位的针灸产生了长期的止痛效果。这一发现表明，电针能使脚踝扭伤的后肢恢复约40%的重量。这种重复性和对针灸的敏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用行为学测试和电生理技术研究电针镇痛中传入神经纤维的来源和纤维大小群。目的2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去甲肾上腺素释放。目的3是测试脚踝扭伤是否诱导脊髓的中枢敏化以及外周伤害性感受器的敏化，以及电针是否降低中枢敏化的水平。目的4是测试电针是否激活脑干去甲肾上腺素能细胞群，进而将去甲肾上腺素释放到脊髓。这项建议的成功完成将揭示脚踝扭伤疼痛的针灸止痛的重要机制。然后，这些知识可以应用于其他形式疼痛条件下的针灸止痛，从而获得洞察力，以建立最有效地利用这种内源性止痛系统的方法。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 an 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 that 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 if EA reduces the level of central sensitization. Aim 4 is to test if EA activates brainstem noradrenergic cell groups, which in turn release NE into 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.