INJURY-INDUCED PAIN--CHEMICAL MODULATION OF NOCICEPTORS

损伤引起的疼痛--伤害感受器的化学调节

• 批准号: 2265904
• 负责人: SRINIVASA N. RAJA
• 金额: $ 22.29万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265904
• 关键词: alpha adrenergic agent; alpha adrenergic receptor; alpha antiadrenergic agent; analgesia; behavioral medicine; bradykinin; clinical trials; clonidine; diagnosis design /evaluation; diagnostic tests; disease /disorder model; heat stimulus; histamine; human subject; hyperalgesia; injury; isoproterenol; laboratory rat; nerve threshold; pain; pain threshold; peripheral nervous system disorders; phentolamine; phenylephrine; placebos; receptor sensitivity; sciatic nerve; sympathectomy; sympathetic nervous system; trauma; ultrasound blood flow measurement

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.

描述：（改编自研究者的摘要）慢性疼痛是一种 影响大部分美国人口的致残疾病。 一种由外伤引起的有趣的疼痛综合症，通常伴有 相关的周围神经损伤，是交感神经维持的疼痛 （SMP）。 SMP 的特点是疼痛和机械和痛觉过敏。 热刺激依赖于交感神经支配 疼痛区域。 根据上次拨款期间取得的预付款， 已经开发了一个模型来解释病理生理学和 SMP 的药理学。 拟议的研究将测试该模型的宗旨 a1 肾上腺素受体在外周组织中发育，从而释放 来自交感神经末梢的去甲肾上腺素激活伤害感受器 并导致疼痛。 平行研究将在患者和 最近开发了大鼠 SMP 神经损伤模型。 拟议的 临床和行为研究将解决两个问题：（1） 外周α-肾上腺素能受体是SMP的罪魁祸首？ 为了回答这个问题 问题，皮内注射产生的疼痛和痛觉过敏 给予α1-、α2-和β-肾上腺素能激动剂和 将在正常受试者和患者中比较肾上腺素能阻滞剂 伴有 SMP 或交感独立性疼痛 (SIP)。 肾上腺素能 SMP 的药理学将通过行为研究进一步表征 在大鼠中使用部分坐骨神经损伤范例。 早期研究 表明该大鼠范例中的疼痛行为是 同情地维持着。 拟议的行为研究还将 提供有关交感神经之间相互作用位点的信息 传出纤维和躯体传入纤维。 (2) 可以α-肾上腺素能 药物可用于诊断SMP吗？ 在过去的授予期内， 根据获得的疼痛缓解情况开发了 SMP 诊断测试 静脉注射酚妥拉明期间。 在提议的 研究表明，SMP 局部用药后可缓解疼痛和痛觉过敏 可乐定的给药将作为一种侵入性较小的方法进行研究 诊断工具。 拟议的研究将带来更好的结果 了解 SMP 的病理生理学和药理学，并了解 开发更具体的诊断测试和药理学 缓解这种衰弱患者的疼痛和痛觉过敏的疗法 疼痛状态。