CAPSAICIN HYPERALGESIA

辣椒素痛觉过敏

• 批准号: 6273708
• 负责人: JON DAVID LEVINE
• 金额: $ 16.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273708
• 关键词: C fiber; capsaicin; dorsal root; electrophysiology; ganglions; hyperalgesia; laboratory rat; local anesthesia; nerve injury; neuronal transport; pain; sensory receptors; sympathectomy

We propose to study peripheral mechanisms that underlie hyperalgesia induced by intradermal injection of the C-fiber excitotoxin capsaicin. In humans such injection produces burning pain with characteristics similar to neuropathic pain syndromes. To investigate our hypothesis that capsaicin-induced primary and secondary hyperalgesia depend on interactions between primary afferent neurons and sympathetic postganglionic neurons, we will use a model of capsaicin-induced hyperalgesia in the rat. First, we will perform behavioral experiments to characterized the time course and dose-dependence of capsaicin-induced primary and secondary hyperalgesia, and to determine if maintenance of the hyperalgesia depends on ongoing activity in primary afferents. We will also determine if capsaicin-evoked primary hyperalgesia is sympathetic-dependent. Second, electrophysiological studies of single dorsal root nerve fibers will examine changes in primary afferent activity during capsaicin- induced hyperalgesia and investigate the role of the sympathetic postganglionic neuron in these changes. We will inject local anesthetic into the skin to determine the extent to which secondary hyperalgesia depends on capsaicin-evoked activity that originates from the area of primary hyperalgesia. We will also determine the contribution of SPGN activity to the electrophysiological changes that accompany primary and secondary hyperalgesia with experiments in which peripheral sympathetics are ablated or stimulated. Third, electrophysiological and anatomical studies will determine if activity of sympathetic postganglionic neurons increases during capsaicin-induced hyperalgesia, and if small-diameter DRG neurons can stimulate such activity. Finally, we will perform behavioral, electrophysiological, and anatomical experiments to localize the site of sympatho-sensory interaction and to characterize its adrenergic pharmacology. The experiments will determine if the site of interaction occurs in the skin or dorsal root ganglion. If the experiments demonstrate that sympatho-sensory interaction occurs in the skin, receptor subtype antagonists will be injected in the skin in regions of primary and secondary hyperalgesia. These studies should provide novel information on the nature of sympatho- sensory interactions in a phenomenon that has numerous characteristics in common with neuropathic pain syndromes in humans. The results will elucidate the importance of primary afferent and sympathetic activity, nature and site of sympatho-sensory interaction, and the relative role of peripheral and central mechanisms in maintaining secondary hyperalgesia. This information will improve our understanding of pain mechanisms, sensory neurophysiology and peripheral sympathetic mechanisms.

我们建议研究基于痛觉过敏的外围机制 通过皮内注射C纤维兴奋毒素辣椒素诱导。 在人类中，这种注射会产生灼痛和特征 类似于神经性疼痛综合征。 调查我们的假设 辣椒素诱导的原发性和次级痛觉过敏取决于 主要传入神经元与同情性之间的相互作用 后神经神经元，我们将使用辣椒素诱导的模型 大鼠中的痛觉过敏。 首先，我们将执行行为实验以表征时间 辣椒素诱导的原发性和次级的疗程和剂量依赖性 Hypergensia，并确定痛苦维持是否取决于 在主要传入中正在进行的活动。 我们还将确定是否 辣椒素诱发的原发性痛觉过敏是交感神经依赖性的。 其次，单背根神经纤维的电生理研究 将检查辣椒素期间初级传入活性的变化 诱发痛觉过敏并研究交感神经的作用 这些变化中的神经节神经元。 我们将注入局部麻醉 进入皮肤以确定次级痛觉过敏的程度 取决于起源于辣椒素诱发的活动 原发性痛觉过敏。 我们还将确定SPGN的贡献 与原发性伴随的电生理变化的活性 次级痛觉过敏，并进行外周交感神经 被消灭或刺激。 第三，电生理学和解剖学研究将确定是否是否 交感神经后神经元的活性在期间增加 辣椒素诱导的痛觉过敏，如果小直径DRG神经元可以 刺激这种活动。 最后，我们将执行行为，电生理和解剖学 实验来定位交感即感官相互作用的位点和 表征其肾上腺素能药理学。 实验将确定 如果相互作用位点发生在皮肤或背根神经节中。 如果实验证明发生交感情感相互作用 在皮肤中，受体亚型拮抗剂将注入皮肤 在原发性和继发性痛觉过敏的区域。 这些研究应提供有关交感性本质的新颖信息 具有许多特征的现象中的感觉互动 与人类的神经性疼痛综合征共同。 结果将 阐明主要传入和交感活动的重要性， 交感情感相互作用的性质和部位，相对角色 维持次级的外围和中央机制 痛苦。 这些信息将改善我们对痛苦的理解 机制，感觉神经生理学和外周交感神经 机制。