NOCICEPTOR SELECTIVE ANALGESIA

也许疼痛系统中最基本的划分是 有髓鞘受体（Asigma）和无髓鞘受体（C） 传入纤维 这两种伤害感受器的激活所引起的疼痛 两种伤害感受器感觉不同， 临床疼痛的不同类型。 以前的工作表明， 这两种伤害感受器类型通过使用 大鼠后爪的不同速率的有害辐射加热。 使用基于这种区别的行为测量模型， 以前支持的工作也表明了在 镇痛治疗，如阿片类药物，对伤害感受性的影响 由这两种伤害感受器引起的反应。 本报告中提出的工作 应用程序将通过检查和比较 神经化学和神经药理学的两种伤害感受器类型在 第一个突触，因为它们向中枢神经系统传递信息。 这将通过测量推定的 来自突触前末梢的神经递质和随后的激活 突触后细胞上的神经递质受体， 选择性激活Asigma或C纤维伤害感受器。 在这 不同的伤害感受器对神经递质的不同使用 类型可以确定。 此外，肾上腺素能、去甲肾上腺素能和 阿片类药物将用于确定是否部分 这些药物的伤害感受器选择性镇痛作用可能是通过 通过抑制突触前神经递质的释放 伤害感受器的脊髓末梢 这些研究将提供 重要的信息，作为差异的机制 调节Asigma和C纤维介导的伤害性感受。 由于这两 伤害感受器的类型可能介导不同种类的临床疼痛， 更好地了解它们的基本性质， 针对特定类型疼痛的镇痛药物， 需要广泛的镇痛方法，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.