INJURY INDUCED PAIN--CHEMICAL MODULATION OF NOCICEPTORS

描述：（改编自研究者摘要）慢性疼痛是一种 影响大部分美国人口的致残性疾病。 一种有趣的疼痛综合征，由创伤引起，通常伴有 伴随周围神经损伤，是交感神经维持性疼痛 （SMP）。 SMP的特征在于对机械性和机械性疼痛的疼痛和痛觉过敏， 热刺激，依赖于交感神经支配的 疼痛区域 根据上一个赠款期间的预付款， 已经开发了一种模型来解释病理生理学， SMP的药理学。 拟议的研究将测试该模型的一个原则 肾上腺素受体在外周组织中发育， 交感神经末梢释放的去甲肾上腺素会激活伤害感受器 导致疼痛 平行研究将在患者和 最近开发的大鼠SMP神经损伤模型。 拟议 临床和行为研究将解决两个问题：（1）是一个 外周α-肾上腺素能受体是SMP的罪魁祸首？ 回答这个 问题，皮内注射产生的疼痛和痛觉过敏 施用α 1-、α 2-和β-肾上腺素能激动剂， 将在正常受试者和患者中比较肾上腺素能阻滞剂 SMP或交感神经独立性疼痛（SIP）。 肾上腺素能 SMP的药理学将通过行为学研究进一步表征 在大鼠中使用部分坐骨神经损伤范例。 早期研究 已经表明，在这种大鼠模型中， 同情地维持着。 拟议的行为研究还将 提供关于交感神经系统之间相互作用的部位的信息， 传出纤维和躯体传入纤维。 (2)α-肾上腺素能 药物可用于SMP的诊断？ 在过去的拨款期间， 根据获得的疼痛缓解情况， 在静脉注射酚妥拉明的过程中 拟议 研究，缓解疼痛和痛觉过敏的SMP后，局部 可乐定的给药将作为一种侵入性较小的 诊断工具。 拟议的研究将导致更好的 了解SMP的病理生理学和药理学， 开发更具体的诊断测试和药理学 用于减轻这种衰弱性疼痛和痛觉过敏的疗法 疼痛状态

Description: (Adapted from investigator's abstract) Chronic pain is a disabling disease that affects a large proportion of the U.S. population. An intriguing pain syndrome that results from trauma, often with associated peripheral nerve injury, is sympathetically maintained pain (SMP). SMP is characterized by pain and hyperalgesia to mechanical and thermal stimuli that are dependent on sympathetic innervation of the painful region. Based on advances made during the last granting period, a model has been developed to explain the pathophysiology and pharmacology of SMP. The proposed studies will test a tenet of the model that a1 adrenoceptors develop in peripheral tissues such that the release of norepinephrine from the sympathetic terminals activates nociceptors and leads to pain. Parallel studies will be done in patients and in a recently developed nerve injury paradigm for SMP in rats. The proposed clinical and behavioral studies will address two questions: (1) Is a peripheral a-adrenergic receptor the culprit in SMP? To answer this question, the pain and hyperalgesia produced by intradermally administered alpha1-, alpha2- and beta-adrenergic agonists and a adrenergic blockers will be compared in normal subjects and in patients with SMP or with sympathetically independent pain (SIP). The adrenergic pharmacology of SMP will be further characterized with behavioral studies in rat using a partial sciatic nerve injury paradigm. Earlier studies have indicated that the pain behavior in this rat paradigm is sympathetically maintained. The proposed behavioral studies will also provide information about the site of interaction between the sympathetic efferents and the somatic afferent fibers. (2) Can alpha-adrenergic drugs be used in the diagnosis of SMP? During the past granting period, a diagnostic test for SMP was developed based on the pain relief obtained during intravenous administration of phentolamine. In the proposed studies, the relief of pain and hyperalgesia in SMP following topical administration of clonidine will be investigated as a less invasive diagnostic tool. The proposed studies will lead to a better understanding of the pathophysiology and pharmacology of SMP and to the development of more specific diagnostic tests and pharmacological therapies for alleviating the pain and hyperalgesia in this debilitating pain state.