NOCICEPTIVE TRANSMISSION IN THE SPINAL CORD

该计划的长期目标是澄清，在不连续的领域 脊髓，候选递质之间的相互关系 似乎与疼痛和止痛有关。P物质(SP) 兴奋性氨基酸(EAA)似乎参与疼痛- 传导和内源性镇痛。我们目前使用的是 生化、解剖学和行为学方法的结合 重点研究这些化合物在疼痛和止痛中的作用。 我们目前关于SP的工作的目标是确定其机制 对SP的脱敏作用。然后可能会设计出止痛药 它们模仿或利用这种脱敏作用。具体的 目标是将SP脱敏的变化与 特定SP代谢物和SP中SP浓度的变化 有约束力的。我们进行地产代理监管局研究的目的，是要阐明 EaS在沿着主要传入和/或传输中播放 中枢投射纤维参与疼痛传递和 确定这种EAA神经传递是否特异地 受阿片和非阿片类化合物的影响。具体的 目的是表征分布(免疫染色)， 浓度(高效液相色谱)和释放(钾引起的变化 细胞外液)在中枢神经系统区域可能是 参与疼痛传递及其与内源性疼痛的关系 发生的抗伤害性机制。 我们的长期计划是扩大我们目前的研究检查 伤害性和抗伤害性过程中的递质释放 在脊髓的不连续区域进行加工。系统 目前在我们实验室使用的是一种植入 半透性透析管穿过脊髓和 为我们提供了一种很好的检测细胞外的方法 液体作为变送器释放的反射。化合物或 被认为可以改变疼痛或递质释放的维持作用 然后在体内进行测试。而我们目前的研究重点是房地产经纪人协会 在大鼠脊髓中释放，我们的长期目标是使用更大的 物种，如猫，不仅检查EaAs的释放，而且 还有更多的SP、SP代谢物和5-羟色胺 不连续的区域和同时来自任何两个不同区域。 所描述的实验将整合我们目前的研究 计划，并扩大其范围。这项研究将有助于 我们对SP和EaS对神经传递的理解。

The long term goal of this plan is to clarify, in discrete areas of the spinal cord, the interrelationships of transmitter candidates that appear to be involved in pain and analgesia. Substance P (SP) and excitatory amino acids (EAA) appear to participate in pain- transmission and endogenous analgesia. We are currently using a combination of biochemical, anatomical and behavioral approaches to focus on the roles of these compounds in pain and analgesia. The goal of our present work on SP is to determine the mechanism of desensitization to SP. Analgesic drugs may then be designed which mimic or exploit such desensitization. The specific objectives are to correlate changes in desensitization to SP with changes in the concentration of specific SP metabolites and in SP binding. The goals of our EAA studies are to elucidate the role that EAAs play in transmission along primary afferent and/or centrally projecting fibers involved in pain-transmission and to determine whether such EAA neurotransmission is specifically affected by opioid and non-opioid compounds. The specific objectives are to characterize the distribution (immunostaining), concentration (HPLC) and release (potassium-evoked changes in extracellular fluid) of EAAs in areas of the CNS presumed to be involved in pain transmission and their relation to endogenously occurring antinociceptive mechanisms. Our long term plans are to extend our present research examining transmitter release during nociceptive and antinoceptive processing in discrete areas of the spinal cord. The system currently in use in our laboratory involves the implantation of a semipermeable dialysis tubing through the spinal cord and provides us with an excellent method of examining extracellular fluid as a reflection of transmitter release. Compounds or mainpulations presumed to alter pain or transmitter release can then be tested in vivo. While our present studies focus on EAA release in the rat spinal cord, our long term goal is to use larger species, such as cat, to examine the release of not only EAAs but also that of SP, SP metabolites and serotonin from even more discrete regions and from any two distinct areas simultaneously. The experiments described will integrate our current research programs and expand their scope. This research will contribute to our understanding of neurotransmission by SP and EAAs.