LBP WITH RADICULOPATHY--AN INFLAMMATORY RESPONSE

描述（改编自申请人的摘要）：腰痛是一种 主要的临床问题仅次于普通感冒在其财政和 对人类痛苦的症状性影响。 长期目标是 了解腰痛的病理生理机制，或 无相关腰神经根病。 为了实现这一目标，我们将 腰椎神经根病和慢性腰椎病动物模型的应用体会 神经病理性疼痛来评估和测试假设。 工作 假设神经根损伤导致炎性脊髓损伤， 引起腰痛临床综合征的细胞因子应答和/或 神经根病 这一假设将在拟议的具体 目的：1）研究脊髓和背根神经节（DRG）的促炎性反应 细胞因子（白细胞介素（IL）-1b，IL-6和肿瘤坏死因子- a（TNF-α）） 蛋白和mRNA的表达水平。 2)评价 当促炎细胞因子（IL-1b， IL-6和TNF-α）局部应用于大鼠的腰神经根。 第三章 比较一般性和特异性细胞因子抑制剂对根的影响 采用硬膜外麻醉， 硬膜内（DRG近端）或神经外（DRG远端）途径 药物输送 这一目标将有助于指导临床问题， 确定最有效的药物输送途径，用于治疗腰椎疼痛 神经根病 4)确定协同或功能缺陷时 与局部麻醉剂联合使用。 解决这些 具体目标，作者建议使用定量免疫组织化学 (IHC)原位杂交（ISH）、电生理学和伤害感受性 （疼痛）行为测定。 其目的是，项目完成后， 将提供： 脊髓促炎细胞因子的体内动力学信息 在神经根病模型中的表达和产生。 指导和支持新药物治疗的初步数据 急性腰痛。 神经免疫反应与神经细胞凋亡关系的新认识 根性损伤和腰痛的临床现象。 指导未来研究的初步数据， 神经免疫反应在神经根性下腰痛病因中的作用 中枢性神经损伤发病机制的新认识 或背根神经节的外周（临床相关的解剖学 位置）。 这些新知识将指导小说的发展， 慢性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.