LBP with Radiculopathy: An Inflammatory Response

描述（由申请人提供）： 腰痛是一个主要的临床问题，仅次于普通感冒， 对人类痛苦的财政和症状影响。我们长远的目标是 了解下腰痛的病理生理机制， 腰椎神经根病为了实现这一目标，我们将运用经验， 腰椎神经根病和慢性神经病理性疼痛的动物模型，以评估 来验证我们的假设在目前的提案中，我们应用来自 上一个资助期调查以下假设：腰神经 根损伤产生CNS免疫介质失衡，导致 “自身免疫性”综合征，继而表现为持续性神经根疼痛。的 在本申请中提出的研究，当与我们先前的研究结合时， 数据，将决定个人的角色和集体的相互作用， 特异性细胞因子和趋化性细胞因子（趋化因子）和细胞运输 持续性神经根痛的病因学核心假设是 通过使用我们实验室的既定方法进行测试，以调查 具体目标： 1.评估趋化因子在持续性神经根痛病因学中的作用 使用铬性腰椎神经根病（C-LR）啮齿动物模型。 2.继续强调损伤部位与DRG关系的重要性 痛苦的产生。 3.确定细胞是否从外周进入中枢神经 系统响应腰神经根损伤，导致持续性 神经根痛 4.评估机械性根损伤与化学性根损伤的作用 炎性成分在神经根疼痛的产生。 5.确定选择性和全面免疫抑制治疗对 改变感觉处理和中枢炎症的可能性 级联。 完成后，该项目将提供：体内动力学信息 脊髓促炎细胞因子和趋化因子的表达和生产， 啮齿动物神经根病模型;指导和支持新的 急性和慢性腰痛的药物治疗; 神经根损伤后的神经免疫反应与神经元损伤的关系 腰痛的临床现象;指导未来研究的初步数据 评估中枢神经免疫激活在导致低 背痛伴神经根病;关于发病机理区别的新信息 背根神经节（a）的中枢或外周神经损伤之间 临床相关的解剖位置）。这些新知识将指导 开发新的非成瘾性预防性疗法和治疗方法， 慢性腰痛

DESCRIPTION (provided by applicant): Low back pain is a major clinical problem second only to the common cold in its financial and symptomatic impact on human suffering. Our long-term objective is to understand the pathophysiological mechanisms of low back pain associated with lumbar radiculopathy. To achieve this goal, we will apply experience with animal models of lumbar radiculopathy and chronic neuropathic pain to evaluate and test our hypothesis. In the current proposal, we apply data from the previous funding period to investigate the following hypothesis: Lumbar nerve root injury produces a CNS immune mediator imbalance, which leads to an "autoimmune" syndrome that in turn manifests as persistent radicular pain. The research proposed in the present application, when integrated with our previous data, will determine the individual roles and the collective interactions of specific cytokines and chemotaxic cytokines, (chemokines) and cell trafficking in the etiology of persistent radicular pain. The central hypothesis will be tested by using established methods in our laboratory to investigate the following Specific Aims: 1. Assess the role of chemokines in the etiology of persistent radicular pain using the Chromic Lumbar Radiculopathy (C-LR) rodent model. 2. Continue to address importance of site of injury in relationship to the DRG to pain generation. 3. Determine whether cells traffic from the periphery into the central nervous system in response to lumbar nerve root injury that results in persistent radicular pain. 4. Assess the contribution of mechanical root injury versus chemical inflammatory components in the generation of radicular pain. 5. Determine the effect of selective and global immunosuppressive therapy on the potential to alter sensory processing and on the central inflammatory cascade. When completed, this project will provide: Information on the in vivo kinetics of spinal proinflammatory cytokine and chemokine expression and production in a rodent radiculopathy models; Preliminary data to guide and support new pharmacological treatments of acute and chronic 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 central neuroimmune activation 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.