NOCICEPTOR SELECTIVE ANALGESIA

各种类型的止痛药的疗效和效力通常是 这取决于所使用的疼痛实验模型。例如，药物 作用于5-羟色胺(1a)受体产生强烈的抗伤害感受性作用 热板试验，但无效或产生痛觉过敏效应 甩尾测试。也观察到了类似的差异 通过刺激不同的大脑部位而产生的抗伤害感觉。一 对这些不同影响的解释是，药物或 脑刺激释放的神经递质产生选择性效应 论不同类型伤害性感受器介导的伤害性感受。这样的一个 吗啡的不同作用已被证明，它选择性地 抑制无髓鞘神经元激活产生的伤害性反应 多通道伤害感受器。我们开发了一种啮齿动物行为模型 似乎有选择性地评估由激活的 C-多模式或有髓A-纤维伤害性感受器。初步 实验表明，阿司匹林具有较好的抗伤害作用 5-羟色胺(1a)激动剂和吗啡对 C-多通道伤害性感受器的激活和α2-的优先效应 肾上腺素能受体激动剂对有髓细胞激活所产生的反应 痛觉感受器。我们建议进行行为和电生理测试 实验进一步确立了该模型的选择性。模型 然后将被用来检查阿片剂、血清能和 α-肾上腺素能激动剂和脑干刺激对伤害性感受的影响 激活C-多模式或A伤害性感受器所引起的反应。 为了调查这些试剂的选择性是否由 抑制伤害性感受器传入纤维，我们将确定这些 治疗减少假定的初级传入神经的释放 神经递质。这些研究可以为我们提供对 抗伤害性感受的基本机制由多种 止痛药。此外，这些研究可能会导致发现 临床上具有选择性镇痛作用的药物对疼痛的影响 由不同的伤害性感受器。

The efficacy and potency of various classes of analgesic drugs is often dependent on the experimental model of pain used. For example, drugs that' act at serotonin(1a) receptors produce a strong antinociceptive effect on the hot-plate test, but are ineffective or produce hyperalgesic effects on the tail flick test. Similar differences have been observed for the antinociception produced by stimulation of various brain sites. One explanation for these different effects is that the drugs or the neurotransmitters released by brain stimulation produce selective effects on the nociception mediated by different types of nociceptors. Such a differential effect has been demonstrated for morphine, which selectively inhibits nociceptive responses produced by the activation of unmyelinated polymodal nociceptors. We have developed a rodent behavioral model which appears to selectively assess responses mediated by the activation of either C-polymodal or myelinated A-fiber nociceptors. Preliminary experiments have shown a preferential antinociceptive effect of serotonin(1a) agonists and morphine on responses produced by the activation of C-polymodal nociceptors and a preferential effect of alpha2- adrenoceptor agonists on responses produced by activation of myelinated nociceptors. We propose to perform behavioral and electrophysiological experiments to further establish the selectivity of this model. The model will then be used to examine the effects of opiate, sertonergic, and alpha-adrenergic agonists, and brainstem- stimulation, on nociceptive responses evoked by the activation of either C-polymodal or A nociceptors. To investigate whether the selectivity of these agents is mediated by inhibition of nociceptor afferent fibers, we will determine whether these treatments reduce the release of putative primary afferent neurotransmitters. These studies could provide important insights into the basic mechanisms underlying the antinociception produce by a variety of analgesic drugs. In addition, these studies may lead to the discovery of clinically useful drugs with selective analgesic effects on pain mediated by different nociceptors.