SYMPATHETIC AND ADRENERGIC DEPENDENCY OF NEUROPATHIC PAIN

这项提案的长期目标是揭示 使疼痛的神经性疾病致残，如灼痛症。虽然很精确 机制尚不清楚，神经病理性疼痛可分为两种类型 基于共鸣依赖的区别：同情地保持 疼痛(SMP)和交感神经非依赖性疼痛(SIP)。近年来， 已经发展了几种动物模型来研究这种机制。 神经性疼痛。其中一些型号似乎代表了SMP，而另一些型号则 代表SIP。本提案使用这些模型来调查 交感神经系统在神经病理性疼痛中的作用。三 提出了具体的目标。第一个目标是检验这样一个假设 周围神经近端损伤导致SMP和远端损伤 诱导SIp。这将在3个神经病理性疼痛模型中进行测试 不同地点的伤害，使用行为测试， 免疫组织化学和电生理方法。第二，测试 假设SMP和SIP都由以下共同机制维护 异位放电传入引起的脊髓敏感化 损伤的感觉神经元，异位放电之间的相关性 3种模型的传入神经元损伤与神经病理性疼痛行为 将首先产生，然后是阻断脊髓传入的效果 疼痛行为的异位放电将被检查。第三，测试 假设某些疼痛状态不受 交感神经的失神经(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 行为测试和电生理方法。 这项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会产生交感依赖 神经病理性疼痛；2)建立不同动物模型的局限性 神经病理性疼痛(这有助于选择实验模型 研究)；及3)引入“上瘾维持”的概念 此外，目前的提议将具有重要的临床意义 其含义在于它可能导致改进的诊断分类 神经病理性疼痛患者的情况，这将有助于确定治疗 战略。

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.