SYMPATHETIC AND ADRENERGIC DEPENDENCY OF NEUROPATHIC PAIN

这项提案的长期目标是揭示 致残性疼痛性神经性疾病，如头痛。 尽管准确 机制尚不清楚，两种类型的神经性疼痛可以是 基于交感依赖性区分：交感维持 疼痛（SMP）和交感神经不依赖性疼痛（SIP）。 近年来， 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，而另一些模型则代表 代表SIP。 本提案使用这些模型来调查 交感神经系统在神经性疼痛中的作用。 三 提出了具体目标。 第一个目标是检验假设， 周围神经近端损伤诱发SMP和远端损伤 诱导SIP。 这将在3种神经性疼痛模型中进行测试， 在不同的位置受伤，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都是由一个共同机制来维护的， 脊髓致敏由输入异位放电引起， 损伤的感觉神经元， 损伤的传入神经元和神经病理性疼痛行为 将首先产生，然后阻断脊髓输入的效果， 将检查疼痛行为的异位放电。 第三，测试 假设某些疼痛状态不受 去交感神经支配（SIP）可能仍然依赖于肾上腺素能 受体，肾上腺素能依赖性将在3种模型中使用 行为测试和电生理方法。 成功完成本建议书预计将实现3个目标： 1)以确定哪种类型的损伤会导致交感神经依赖 神经病理性疼痛; 2）建立各种动物模型的局限性， 神经病理性疼痛（这有助于选择实验模型） 研究）;及3）引入“肾上腺素能维持”的概念 痛苦“此外，目前的建议将具有重要的临床意义， 这意味着它可能导致改进诊断分类 这反过来将有助于确定治疗方法 战略布局

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.