NOCICEPTOR SELECTIVE ANALGESIA

也许疼痛系统中最基本的划分是在感觉之间 有髓细胞受体(Asigma)和无髓细胞受体(C) 传入纤维。激活这两种伤害性感受器引起的疼痛 类型感觉不同，两种伤害性感受器类型已被牵连 在不同的临床疼痛中。以前的工作表明， 这两种伤害性感受器类型通过使用 对大鼠后爪进行不同程度的伤害性辐射加热。 使用基于这一区别的行为止痛模型， 以前得到支持的工作也显示出明显的差异 阿片类等止痛治疗对伤害性感受器的影响 由这两种伤害性感受器类型引起的反应。在本报告中提出的工作 应用程序将通过检查和比较 两种伤害性感受器的神经化学和神经药理学 首先是突触，因为它们向中枢神经系统传递信息。 这将通过测量推定的 突触前终末的神经递质及其随后的激活 突触后细胞上神经递质受体的表达 选择性激活Asigma或C纤维伤害性感受器。在这 不同伤害性感受器对神经递质的不同使用 可以确定类型。此外，5-羟色胺能、去甲肾上腺素和 将应用阿片类药物来确定是否有部分 这些药物的伤害性选择性镇痛作用可能是通过介导的。 通过抑制突触前神经递质的释放 伤害性感受器的脊椎终末。这些研究应该提供 作为差异背后的机制的重要信息 Asigma和C纤维的调制介导伤害性感受。因为这两个人 伤害性感受器的类型可能介导了不同类型的临床疼痛， 更好地了解它们的基本性质应该会导致更好的 针对特定类型的疼痛的止痛药，减少 需要广泛的止痛方法，例如全身应用 鸦片类药物。

Perhaps the most basic division in the pain system is between sensory receptors with myelinated (Asigma) and those with unmyelinated (C) afferent fibers. Pain evoked by the activation of these two nociceptor types feels different and the two nociceptor types have been implicated in different kinds of clinical pain. Previous work demonstrated that these two nociceptor types are differentially activated by using different rates of noxious radiant heating of the hindpaw of the rat. Using a behavioral analgesiometric model based on this distinction, the previous supported work also demonstrated clear differences in the effects of analgesic treatments, such as opiates, on nociceptive responses evoked by these two nociceptor types. Work proposed in this application would extend this study by examining and comparing the neurochemistry and neuropharmacology of the two nociceptor types at the first synapse as they convey information to the central nervous system. This will be accomplished by measuring the release of putative neurotransmitters from presynaptic terminals and subsequent activation of neurotransmitter receptors on postsynaptic cells as evoked by selective activation of either Asigma or C fiber nociceptors. In this way, the differential use of neurotransmitters by different nociceptor types can be determined. In addition, serotonergic, noradrenergic, and opioid agents will be applied to determine whether part of the nociceptor-selective analgesic effects of these agents may be mediated through inhibition of the release of neurotransmitters from presynaptic spinal terminals of the nociceptors. These studies should provide important information as the mechanisms underlying the differential modulation of Asigma and C fiber mediated nociception. Since these two types of nociceptors probably mediate different kinds of clinical pain, a better understanding of their basic properties should lead to better targeting of analgesic drugs for specific types of pain, reducing the need for broad analgesic approaches, such as systemic application of opiates.