NOCICEPTIVE TRANSMISSION IN THE SPINAL CORD

脊髓中的伤害性传播

• 批准号: 3069494
• 负责人: ALICE A LARSON
• 金额: $ 7万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3069494
• 关键词: afferent nerve; aminoacid; analgesia; analgesics; cats; extracellular matrix; high performance liquid chromatography; laboratory mouse; laboratory rat; neural transmission; neurotransmitter metabolism; pain; serotonin; spinal cord; substance P

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.

该计划的长期目标是在离散领域澄清 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） 和兴奋性氨基酸（EAA）似乎参与疼痛- 传递和内源性镇痛。 我们目前正在使用 结合生物化学、解剖学和行为学方法 关注这些化合物在疼痛和镇痛中的作用。 我们目前关于SP的工作的目标是确定其机制 然后可以设计镇痛药物， 其模仿或利用这种脱敏。 具体 目的是将对SP脱敏的变化与 特定SP代谢物浓度和SP 约束力 我们EAA研究的目的是阐明 EAA在沿着初级传入和/或 中枢投射纤维参与疼痛传递， 确定这种EAA神经传递是否特异性地 受阿片类和非阿片类化合物的影响。 具体 目的是表征分布（免疫染色）， 浓度（HPLC）和释放（钾诱发的变化， 细胞外液）的EAA在中枢神经系统的地区，推测是 参与疼痛传递及其与内源性 产生抗伤害感受机制。 我们的长期计划是扩大我们目前的研究范围 在伤害感受和抗伤害感受期间的递质释放 在脊髓的离散区域进行处理。 系统 目前在我们的实验室中使用的涉及植入一种 通过脊髓的半渗透性透析管， 为我们提供了一个很好的方法来检查细胞外 液体作为发射器释放的反映。 化合物或 假定能改变疼痛或递质释放的刺激， 然后在体内进行测试。 虽然我们目前的研究主要集中在EAA 释放在大鼠脊髓，我们的长期目标是使用较大的 物种，如猫，不仅检查EAA的释放， 也就是SP，SP代谢物和血清素， 分离的区域和同时来自任何两个不同的区域。 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EAA神经传递的理解。