LBP WITH RADICULOPATHY--AN INFLAMMATORY RESPONSE

描述(根据申请者的摘要改编)：腰痛是一种 在经济和社会发展方面仅次于普通感冒的重大临床问题 对人类痛苦的症状影响。长期目标是 了解腰背痛的病理生理机制 没有相关的腰椎神经根病。为了实现这一目标，我们将 腰神经根病和慢性腰神经根病动物模型的应用体会 神经病理性疼痛来评估和检验这一假设。在工作中 假设神经根损伤会导致脊髓发炎 引起下腰痛和/或临床综合征的细胞因子反应 神经根病。这一假设将在拟议的具体方案中得到检验 目的：1)表征脊髓和背根神经节(DRG)的促炎作用 细胞因子(白介素1b、白介素6和肿瘤坏死因子-a) 蛋白质和信使核糖核酸对大鼠神经根损伤的反应。2)评估 促炎症细胞因子(IL-1b、 IL-6和TNF-a)局部应用于大鼠腰神经根。3) 通用和特异性细胞因子抑制剂对根的影响比较 硬膜外给药大鼠的损伤相关疼痛行为和功能状态 硬膜内(背根节近端)或神经外膜(背根节远端)入路 药物递送。这一目的将有助于指导临床问题 确定治疗腰痛的最有效给药途径 神经根病。4)在以下情况下确定协同效应或功能缺陷 与局部麻醉给药结合使用。要解决这些问题 针对特定的目标，作者建议使用定量免疫组织化学 (IHC)和原位杂交(ISH)、电生理和伤害性反应 (疼痛)行为分析。其目的是在完成后，该项目 将提供： 脊髓促炎细胞因子体内动力学的研究进展 神经根病模型中的表达和产物。 指导和支持新的药物治疗的初步数据 急性腰背痛。 对神经免疫反应与神经功能关系的新认识 牙根损伤和腰背痛的临床现象。 初步数据，以指导未来评估影响的研究 神经根病引起的下腰痛的神经免疫反应。 中枢神经损伤的病因学鉴别新信息 或背根神经节的周围(临床相关的解剖学 位置)。这一新知识将指导小说的发展， 慢性下腰痛的非成瘾性预防性治疗和治疗。

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.