PEPTIDE/MONOAMINE CONTROL OF SPINAL PAIN TRANSMISSION

许多研究表明，腹侧髓质（VM）在麻醉剂 镇痛和刺激产生镇痛。 初步研究 首次报道了一种新发现的下行镇痛 起源于VM的球脊髓P物质（SP）系统。 这种新发现的下行性SP镇痛通路的作用 将在拟定的记录研究中探索疼痛抑制。 SP拮抗剂和5-羟色胺（5-HT）拮抗剂对 阻断VM抑制背角伤害感受单位将是 定量评估，允许量化相对 球脊髓SP和5-HT系统在疼痛中的作用 抑制作用 记录研究的独特设计将允许 初级传入SP输入与球脊髓SP输入对比 输入到同一个背角神经元。 的相互作用 还将探讨球脊髓SP和5-HT系统的记录 使用5，7-DHT处理的动物选择性地破坏 脊髓5-HT纤维 在我们的工作模型中，下行5-HT系统起着重要的作用。 球脊髓SP介导疼痛中重要交互作用 抑制作用 提出了第二组实验， 5-HT受体亚型的定义 用的是球脊髓5-羟色胺镇痛系统 拟定受体 结合和记录研究将描述 5-HT受体亚型（1A或1B）与 下行5-HT镇痛通路。 拟定受体结合 竞争实验将表征背角1A和1B 5-HT受体亚型，并确定最具选择性的1A和1B 激动剂和拮抗剂用于随后的记录研究。 这些记录研究将确定5-HT 1受体 介导背角伤害性单位抑制的亚型 活动 除了这些研究对疼痛的重要性之外， 研究，他们将提供对受体的理解， 结构/功能关系在CNS中很少见到。

Numerous studies implicate the ventral medulla (VM) in narcotic analgesia and stimulation produced-analgesia. Preliminary studies report for the first time a newly identified descending analgesia system originating in VM, the bulbospinal substance P (SP) system. The role of this newly identified descending SP analgesia pathway in pain inhibition will be explored in proposed recording studies. The ability of SP antagonists and serotonin (5-HT) antagonists to block VM inhibition of dorsal horn nociceptive units will be quantitatively assessed, allowing the quantification of the relative contributions of bulbospinal SP and 5-HT systems in pain inhibition. The unique design of the recording studies will permit primary afferent SP input to be contrasted with bulbospinal SP input to the same dorsal horn neuron. The interaction of the bulbospinal SP and 5-HT systems will also be explored in recording studies employing 5,7-DHT treated animals to selectively destroy spinal 5-HT fibers. In our working model the descending 5-HT system plays an important interactive role in bulbospinal SP-mediated pain inhibition. A second group of experiments are proposed to pharmacologically define the 5-HT receptor subtype associated with this bulbospinal 5-HT analgesia system. Proposed receptor binding and recording studies will pharmacologically characterize the 5-HT receptor subtype (1A or 1B) associated with the descending 5-HT analgesia pathway. Proposed receptor binding competition experiments will characterize dorsal horn 1A and 1B 5-HT receptor subtypes and identify the most selective 1A and 1B agonists and antagonists for use in subsequent recording studies. These recording studies will determine the 5-HT1 receptor subtype mediating inhibition of dorsal horn nociceptive unit activity. In addition to the importance of these studies for pain research, they will provide an understanding of receptor structure/function relationships rarely seen in the CNS.