SYMPATHETIC AND ADRENERGIC DEPENDENCY OF NEUROPATHIC PAIN

神经病理性疼痛的交感神经和肾上腺素依赖性

• 批准号: 6338930
• 负责人: JIN M CHUNG
• 金额: $ 10.35万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6338930
• 关键词: C fiber; afferent nerve; alpha adrenergic receptor; alpha antiadrenergic agent; behavior test; behavioral habituation /sensitization; cell cycle; disease /disorder model; efferent nerve; electrophysiology; immunocytochemistry; innervation; laboratory rat; nerve injury; neuroanatomy; neurons; pain; spinal ganglion; sympathetic nervous system

The long-term goal of this proposal is to uncover the mechanisms of disabling painful neuropathic disease, such as causalgia. Although exact mechanisms are not clear, two types of neuropathic pain can be distinguished based on sympathetic dependency: sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). In recent years, several animal models have been developed to investigate the mechanisms of neuropathic pain. Some of these models seem to represent SMP while others represent SIP. The present proposal uses these models to investigate the role of the sympathetic nervous system in neuropathic pain. Three specific aims are proposed. The first aim tests the hypothesis that proximal injury of a peripheral nerve induces SMP and distal injury induces SIP. This will be tested in 3 neuropathic pain models with injuries at different locations, using behavioral testing, immunohistochemical and electrophysiological methods. Second, to test the hypothesis that both SMP and SIP are maintained by a common mechanism of spinal sensitization caused by input of ectopic discharges arising from injured sensory neurons, correlations between ectopic discharges of injured afferent neurons and neuropathic pain behaviors in the 3 models will be made first and then the effects of blocking the spinal input from ectopic discharges on pain behaviors will be examined. Third, to test the hypothesis that certain pain states which are not influenced by denervation of sympathetic nerves (SIP) may still depend on adrenergic receptors, adrenergic dependency will be tested in the 3 models using behavioral tests and electrophysiological methods. Successful completion of this proposal is expected to accomplish 3 goals: 1) to determine which type of injuries produce sympathetically dependent neuropathic pain; 2) to establish limitations of various animal models for neuropathic pain (which is helpful in choosing a model for experimental studies); and 3) to introduce the concept of "adrenergically maintained pain." Furthermore, the present proposal will have an important clinical implication in that it may lead to an improved diagnostic classification of neuropathic pain patients which in turn will help determine treatment strategies.

该提议的长期目标是发现 禁用疼痛的神经性疾病，例如因果关系。 虽然是准确的 机制尚不清楚，两种类型的神经性疼痛可能是 基于同情依赖性而区分：交感神经维护 疼痛（SMP）和同情独立的疼痛（SIP）。 最近几年， 已经开发了几种动物模型来研究 神经性疼痛。 其中一些模型似乎代表SMP，而另一些模型 代表SIP。 本提案使用这些模型调查 交感神经系统在神经性疼痛中的作用。 三 提出了具体目标。 第一个目的检验了以下假设 周围神经的近端损伤会诱导SMP和远端损伤 诱导SIP。 这将在3个神经性疼痛模型中进行测试 使用行为测试在不同位置受伤， 免疫组织化学和电生理方法。 第二，测试 假设SMP和SIP都通过一种常见的机制来维持 由异位放电的输入引起的脊柱敏化 受伤的感觉神经元，异位放电之间的相关性 3个模型中受伤的传入神经元和神经性疼痛行为 将首先制作，然后将脊柱输入从 将检查对疼痛行为的异位放电。 第三，测试 假设某些不受受影响的疼痛状态 交感神经的神经（SIP）可能仍取决于肾上腺素能 受体，肾上腺素能依赖性将在3个模型中使用 行为测试和电生理方法。 预计该提案的成功完成将实现3个目标： 1）确定哪种类型的伤害会产生同情依赖 神经性疼痛； 2）建立各种动物模型的局限 神经性疼痛（这有助于选择实验模型 研究）； 3）介绍“肾上腺素维护的概念 此外，本提案将具有重要的临床 暗示可能会导致改进的诊断分类 神经性疼痛患者又有助于确定治疗 策略。