LBP WITH RADICULOPATHY--AN INFLAMMATORY RESPONSE

腰痛伴神经根病——炎症反应

• 批准号: 6055655
• 负责人: Joyce A De Leo
• 金额: $ 20.93万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-03 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6055655
• 关键词: backache; cytokine; dorsal root; drug delivery systems; electrophysiology; immunocytochemistry; in situ hybridization; inflammation; interleukin 1; interleukin 6; laboratory rat; local anesthesia; lumbar plexus; nerve injury; neuritis; neuroimmunomodulation; pain; spinal ganglion; tumor necrosis factor alpha

DESCRIPTION (Adapted from the Applicant's Abstract): Low back pain is a major clinical problem second only to the common cold in its financial and symptomatic impact on human suffering. The long-term objective is to understand the pathophysiological mechanisms of low back pain with or without associated lumbar radiculopathy. To achieve this goal, we will apply experience with animal models of lumbar radiculopathy and chronic neuropathic pain to evaluate and test the hypothesis. The working hypothesis is that nerve root injury leads to an inflammatory spinal cytokine response that causes the clinical syndrome of low back pain and/or radiculopathy. This hypothesis will be tested in the proposed specific aims: 1) Characterize spinal and dorsal root ganglion (DRG) proinflammatory cytokine (Interleukin (IL)-1b, IL-6 and Tumor Necrosis Factor- a (TNF-a) protein and mRNA in response to nerve root injury in the rat. 2) Evaluate the electrophysiological response when proinflammatory cytokines (IL-1b, IL-6 and TNF-a) are locally applied to lumbar nerve roots in the rat. 3) Compare the effect of general and specific cytokine inhibitors on root injury-related pain behaviors and functional status in rats using epidural, intradural (proximal to the DRG) or epineural (distal to the DRG) routes of drug delivery. This aim will help direct the clinical question of determining the most effective route of drug delivery for painful lumbar radiculopathy. 4) Determine the synergistic or functional deficits when used in combination with local anesthetic administration. To address these specific aims, the authors propose to use quantitative immunohistochemistry (IHC), and in situ hybridization (ISH), electrophysiology and nociceptive (pain) behavioral assays. The intent is that when completed, the project will provide: Information on the in vivo kinetics of spinal proinflammatory cytokine expression and production in radiculopathy models. Preliminary data to guide and support new pharmacological treatments of acute low back pain. New insight into the relationship between the neuroimmune response of nerve root injury and the clinical phenomenon of low back pain. Preliminary data to direct future studies that evaluate the impact of neuroimmune responses in causation of low back pain with radiculopathy. New information on the pathogenetic distinction between nerve injury central or peripheral to the dorsal root ganglion (a clinically relevant anatomical location). This new knowledge will guide development of novel, non-addictive preventive therapies and treatments for chronic low back pain.

描述（改编自申请人的摘要）：下背痛是 主要的临床问题仅次于其财务中的普通感冒和 对人类痛苦的有症状影响。 长期目标是 了解与或 没有相关的腰部根部病。 为了实现这一目标，我们将 利用腰椎肾上腺病和慢性的动物模型的经验 神经性疼痛评估和检验假设。 工作 假设是神经根损伤导致炎症性脊柱 细胞因子反应导致腰痛临床综合征和/或 辐射病。 该假设将在提出的特定特定中进行检验 目的：1）表征脊髓和背根神经节（DRG）促炎 细胞因子（白介素（IL）-1b，IL-6和肿瘤坏死因子A（TNF-A） 蛋白质和mRNA响应大鼠的神经根损伤。 2）评估 促炎细胞因子（IL-1B，， IL-6和TNF-A）局部应用于大鼠的腰神经根。 3） 比较一般和特异性细胞因子抑制剂对根的影响 使用硬膜外麻醉，与损伤有关的疼痛行为和功能状态 内部（DRG近端）或外皮（DRG远端）路线 药物输送。 这个目标将有助于指导临床问题 确定疼痛腰部最有效的药物输送途径 辐射病。 4）确定当时的协同或功能缺陷 与局部麻醉剂结合使用。 解决这些 作者建议使用定量免疫组织化学 （IHC）和原位杂交（ISH），电生理学和伤害感受器 （疼痛）行为测定。 目的是，完成后，该项目 将提供： 有关脊柱促炎细胞因子体内动力学的信息 辐射模型中的表达和产生。 初步数据指导和支持新的药理治疗 急性下腰痛。 对神经神经免疫反应之间关系的新见解 根部损伤和下背痛的临床现象。 初步数据指导未来的研究，以评估 神经免疫性反应在降低了底部疼痛的因果关系中。 有关神经损伤中心之间致病性区别的新信息 或背侧神经节的外围（临床相关的解剖学 地点）。 这些新知识将指导小说的发展， 慢性下背痛的非副作用预防疗法和治疗方法。