MECHANISMS OF HYPERALGESIA IN THE SPINAL DORSAL HORN

脊髓背角痛觉过敏的机制

• 批准号: 2460635
• 负责人: VJEKOSLAV MILETIC
• 金额: $ 14.26万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460635
• 关键词: dorsal horn; hyperalgesia; immunocytochemistry; laboratory rat; long term potentiation; membrane potentials; neural plasticity; neurophysiology; protein kinase C; sciatic nerve

DESCRIPTION (Adapted from the Investigator's Abstract): In this proposal we will employ loose ligation of the sciatic nerve as a model to further our understanding of the mechanisms underlying the pathophysiology of neuropathic pain, a most-puzzling and treatment-resistant type of chronic pain. The overall goal is to determine whether sciatic ligation in rats (as a form of persistent nociception) produces plastic changes in spinal dorsal horn neuronal function that contribute to the observation of thermal hyperalgesia (as an indicator of neuropathic pain). In the first part of this proposal we will examine whether long-term potentiation (LTP) and long-term depression (LTD), as electrophysiological correlates of synaptic plasticity, can be recorded in the superficial spinal dorsal horn of control, sham-operated or ligated rats in vivo. We will monitor extracellular field potentials that are evoked by high-frequency or low-frequency repetitive stimulation of primary afferent fibers, and determine whether synaptic activity and function are modified over the course of several hours. We are especially interested in establishing whether any observed enhancement or diminution in afferent-evoked synaptic function is a normal feature of dorsal horn neuronal activity, or is specifically observed only after sciatic ligation. In the second part of this proposal we are interested in establishing the possible involvement of protein kinase C (PKC) as a critical, if not crucial, biochemical mediator of any sciatic ligation-induced plasticity in the rat spinal dorsal hoary. We will employ biochemical assays to assess whether sciatic ligation modifies the distribution of total PKC activity, and the quantity of its pII (beta-2), y (gamma) and :, (zeta) isozymes in the cytosolic and crude P-2 membrane subcellular fractions of the spinal dorsal horn of control, sham-operated or ligated rats. We will also use immunocytochemical procedures to visualize any injury-induced changes in the pattern of immunocytochemical staining of the PKC ,BII, y, and (, isozymes in the spinal dorsal horn of control, sham-operated or ligated rats. We hope that the studies in this proposal will yield critical information about the processes underlying neuropathic pain, as well as about potential approaches to more effective clinical treatments.

描述（改编自调查员的摘要）：在此提案中，我们 将采用坐骨神经的松散连接作为模型，以进一步 理解对病理生理的机制的理解 神经性疼痛，一种慢性和耐药类型的慢性 疼痛。 总体目的是确定是否在大鼠 一种持续的伤害感受）在脊髓背侧产生塑性变化 角神经元功能有助于观察热 痛觉过敏（作为神经性疼痛的指标）。 在第一部分 该提案我们将研究长期增强（LTP）和 长期抑郁（LTD），作为突触的电生理相关性 可塑性，可以记录在表面的脊柱背角 在体内对照，假手术或连接的大鼠。 我们将监视 高频或 初级传入纤维的低频重复刺激，以及 确定突触活动和功能是否在 几个小时的课程。 我们对建立特别感兴趣 是否有任何观察到的增强性或传入诱发的突触中的减少 功能是背角神经元活动的正常特征，或IS 特别是在坐骨结扎后才观察到。 在本提案的第二部分中，我们有兴趣建立 蛋白激酶C（PKC）可能参与至关重 任何坐骨神经连接诱导的可塑性的至关重要的生化介体 大鼠脊椎背部。 我们将使用生化测定法进行评估 坐骨神经连接是否修改了总PKC活性的分布， 以及其PII（beta-2），y（伽马）和：（Zeta）同工酶的数量 脊柱的胞质和粗P-P-2膜亚细胞分数 背侧控制角，假手术或结扎的大鼠。 我们还将使用 免疫细胞化学程序可视化任何受伤引起的变化 PKC，BII，Y和（同工酶的免疫细胞化学染色的模式 在脊柱背侧对照角，假手术或结扎的大鼠。 我们 希望该提案中的研究将产生有关的关键信息 神经性疼痛以及潜在的过程中的过程 采用更有效的临床治疗方法。