NOCICEPTOR SELECTIVE ANALGESIA

各种类型的镇痛药物的功效和效力通常是不确定的。 这取决于所使用的疼痛实验模型。例如， 作用于5-羟色胺（1a）受体，产生强烈的抗伤害作用， 热板试验，但无效或产生痛觉过敏的影响， 甩尾测试 在以下方面也观察到了类似的差异： 通过刺激大脑的不同部位而产生的抗伤害感受。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 不同类型的伤害感受器所介导的伤害感受。 这样的 已经证明了吗啡的不同作用， 抑制由无髓鞘神经元激活产生的伤害性反应， 多模式伤害感受器我们开发了一种啮齿动物行为模型， 似乎选择性地评估由激活介导的反应， C型多模态或有髓鞘A型纤维伤害感受器。 初步 实验已经显示了优选的抗伤害感受作用， 5-羟色胺（1a）激动剂和吗啡对由 C-多模态伤害感受器的激活和α 2- 肾上腺素能受体激动剂对有髓神经元激活产生的反应的影响 伤害感受器 我们建议进行行为和电生理学检查 实验，以进一步建立该模型的选择性。模型 然后将被用来检查阿片类药物，sertonergic， α-肾上腺素能激动剂和脑干刺激对伤害性 由C-多模态或A伤害感受器的激活引起的反应。 为了研究这些药物的选择性是否由 抑制伤害感受器传入纤维，我们将确定这些是否 治疗减少了假定的初级传入神经的释放 神经传递素这些研究可以提供重要的见解， 抗伤害感受的基本机制是由多种 止痛药此外，这些研究可能会发现 具有选择性镇痛作用的临床有用药物 不同的伤害感受器。

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.