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.

该提案的长期目标是揭示 使痛苦的神经性疾病失效，例如灼痛。 虽然准确 机制尚不清楚，可分为两种类型的神经性疼痛 基于同情依赖来区分：同情地维持 疼痛（SMP）和交感独立性疼痛（SIP）。 最近几年， 已开发出多种动物模型来研究其机制 神经性疼痛。 其中一些模型似乎代表 SMP，而另一些则代表 代表SIP。 本提案使用这些模型来研究 交感神经系统在神经性疼痛中的作用。 三 提出了具体目标。 第一个目标检验以下假设： 周围神经近端损伤诱发 SMP 和远端损伤 诱发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学方法。 其次，要测试 假设 SMP 和 SIP 都是由一个共同的机制来维护的 因异位放电输入引起的脊髓敏化 受伤的感觉神经元，异位放电之间的相关性 3 个模型中传入神经元受损和神经性疼痛行为 首先会产生阻塞脊髓输入的效果 将检查异位放电对疼痛行为的影响。 三、测试 假设某些疼痛状态不受 交感神经去神经支配（SIP）可能仍依赖于肾上腺素能 受体，肾上腺素能依赖性将在 3 个模型中使用进行测试 行为测试和电生理学方法。 该提案的成功完成预计将实现 3 个目标： 1）确定哪种类型的伤害产生交感依赖性 神经性疼痛； 2）建立各种动物模型的局限性 神经性疼痛（这有助于选择实验模型 研究）； 3）引入“肾上腺素维持 疼痛。”此外，本提案将具有重要的临床意义 这意味着它可能会导致诊断分类的改进 神经性疼痛患者的情况，这反过来将有助于确定治疗方法 策略。