TRIGEMINAL NEURONS--SUSTAINED RESPONSE TO OPOIDS

描述（研究者摘要）：本研究的长期目标 确定阿片类药物对伤害感受的作用的细胞机制 （疼痛）神经元。 因为阿片类药物是最有效的药物之一 它们可以缓解疼痛，被认为是抑制剂。 然而，还有 许多阿片类药物对人产生直接兴奋作用的例子 伤害感受神经元。 阿片类药物的临床重要特征之一 镇痛作用是阿片类药物在缓解炎症方面非常有效 痛，但对神经性疼痛无效。 此次资助的重点是 确定阿片类药物引起的兴奋反应的作用 炎症和神经性疼痛状态。 申请人假设 阿片类药物的作用是兴奋性和抑制性作用之间的平衡 阿片类药物对炎症的作用与相反的作用之间的主要区别 神经病理性疼痛的关键在于平衡倾向于兴奋性疼痛 一侧处于神经病理状态。 为了检验这个假设，他们将 (1) 比较阿片类药物影响兴奋性和抑制性的机制 从正常、发炎的背角神经元中分离出的氨基酸反应 （即关节炎）和神经病动物，以及（2）比较 阿片类药物对背角神经元和初级传入神经元 Ca2+ 动员的影响 这些动物的终点站。 实验将在单个 背角神经元和脊髓切片。 膜电流将为 用穿孔贴片电极监测；细胞内Ca2 浓度将使用荧光 Ca2 指示来测量。 这些实验将提供有关潜在机制的信息 阿片类药物对正常、炎症和神经病变的兴奋作用 州。 这些知识将帮助我们开发新药和更好的药物 治疗疼痛的策略。 此外，该研究将 有助于更好地理解可塑性背后的机制 一般的伤害感受系统。

DESCRIPTION (Investigator's Abstract): The long term goal of this research is the determination of cellular mechanisms of opioid actions on nociceptive (pain) neurons. Because opioids are among the most effective agents for relieving pain, they are thought of as inhibitory agents. Yet, there are many examples in which opioids exert direct excitatory actions on nociceptive neurons. One of the clinically important features of opioid antinociception is that opioids are very effective in relieving inflammatory pain, but are ineffective for neuropathic pain. The focus of this grant is to determine the role(s) of the opioid-induced excitatory responses in inflammatory and neuropathic pain states. The applicants hypothesize that opioid actions are a balance between excitatory and inhibitory effects and a major difference between the actions of opioids on inflammatory as opposed to neuropathic pain is that the balance is tipped towards the excitatory side in the neuropathic state. To test this hypothesis, they will (1) compare the mechanisms by which opioids affect excitatory and inhibitory amino acid responses in dorsal horn neurons isolated from normal, inflamed (i.e., arthritic) and neuropathic animals, and (2) compare the effects of opioids on Ca2+ mobilization in dorsal horn neurons and in primary afferent terminals of these animals. The experiments will be performed on single dorsal horn neurons and spinal cord slices. The membrane currents will be monitored with perforated patch electrodes; the intracellular Ca2+ concentrations will be measured using fluorescence Ca2+ indications. These experiments will provide information about the mechanisms underlying excitatory actions of opioids in the normal, inflammatory and neuropathic states. The knowledge will aid us in developing new drugs and better strategies for the treatment of pain. In addition, the study will facilitate a better understanding of mechanisms underlying the plasticity in nociceptive systems in general.