MECHANISMS OF PERIPHERALLY-MEDIATED NICOTINIC ANALGESIA

拟进行的研究将检验神经元烟碱受体激动剂在外周作用部位产生抗伤害感受的假设。 这些研究的具体目的是评估完全弗氏佐剂（CFA）和慢性压迫性损伤（CCI）实验性疼痛模型中神经元烟碱受体激活的抗伤害效应。 此外，分子生物学技术将用于确定神经元烟碱受体的表达和分布，沿着外周感觉神经元的过程中起源于三叉神经节。 还将评估在炎性和神经性实验性疼痛条件下对神经元烟碱受体表达的影响以及这些改变依赖于神经生长因子的程度。 因此，本研究将检查外周神经元烟碱受体在烟碱受体激动剂的抗伤害效应中所起的作用。 由于这些药物的不良副作用及其在某些类型的神经性疼痛中的无效性，开发具有与阿片类或非甾体抗炎药（NSAIDS）不同的机制的镇痛药是重要的。 建立烟碱类镇痛药的外周作用位点具有消除中枢作用烟碱类镇痛药的任何潜在中枢神经系统副作用的优势。

The proposed studies will test the hypothesis that neuronal nicotinic receptor agonists produce antinociception at peripheral sites of action. The specific aims of these studies will be to assess the antinociceptive effects of neuronal nicotinic receptor activation in the complete Freund's adjuvant (CFA) and chronic constriction injury (CCI) models of experimental pain. In addition, molecular biological techniques will be utilized to determine the expression and distribution of neuronal nicotinic receptors along peripheral sensory neuronal processes originating in the trigeminal ganglion. The effects on neuronal nicotinic receptor expression under conditions of inflammatory and neuropathic experimental pain and the extent to which these alterations are dependent upon nerve growth factor will also be assessed. Thus, the present studies will examine the role that peripheral neuronal nicotinic receptors play in the antinociceptive effects seen due to nicotinic agonists. The development of analgesic drugs with distinct mechanisms than those of opioids or non-steroidal anti inflammatory drugs (NSAIDS) is important due to the undesirable side effects of these drugs and their ineffectiveness in certain types of neuropathic pain. Establishing a peripheral site of action for nicotinic analgesic drugs holds out the advantage of eliminating any potential central nervous system side effects of centrally acting nicotinic analgesics.