TRIGEMINAL NEURONS--SUSTAINED RESPONSE TO OPOIDS

描述(研究人员摘要)：本研究的长期目标 是阿片类药物对伤害性感受作用的细胞机制的确定 (疼痛)神经元。因为阿片类药物是最有效的药物之一 它们被认为是抑制剂，可以缓解疼痛。然而，还有一些 阿片类药物对人体产生直接兴奋作用的许多例子 伤害性神经元。阿片类药物的临床重要特征之一 抗伤害性是阿片类药物在缓解炎症方面非常有效。 止痛，但对神经性疼痛无效。这笔赠款的重点是 确定阿片类药物兴奋反应在中枢神经系统中的作用(S) 炎症性和神经性疼痛状态。申请者假设 阿片类药物的作用是兴奋和抑制效应之间的平衡， 阿片类药物抗炎作用与非阿片类药物的主要区别 神经病理性疼痛是天平向兴奋性倾斜 一边处于神经病的状态。为了检验这一假设，他们将(1) 比较阿片类药物影响兴奋性和抑制性的机制 正常、炎症状态下分离的背角神经元氨基酸反应 (例如，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细胞内钙离子动员的影响 这些动物的终端。这些实验将在单个 背角神经元和脊髓切片。膜电流将是 穿孔贴片电极监测；细胞内钙离子 浓度将使用荧光钙指示剂进行测量。 这些实验将提供有关潜在机制的信息 阿片类药物在正常、炎症和神经病理性疾病中的兴奋作用 各州。这些知识将帮助我们开发新药和更好的 治疗疼痛的策略。此外，这项研究将 有助于更好地理解塑性的潜在机制 一般情况下，伤害性感受系统。

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.