LBP with Radiculopathy: An Inflammatory Response

描述(由申请人提供)： 腰背痛是仅次于普通感冒的主要临床问题。 对人类苦难的财政和症状影响。我们的长期目标是 了解下腰痛的病理生理机制 患有腰椎神经根病。为了实现这一目标，我们将运用以下经验 腰神经根病和慢性神经病理性疼痛动物模型的评价 来检验我们的假设。在当前的提案中，我们应用来自 以前的资助期调查了以下假说：腰神经 根损伤会导致中枢神经系统免疫介质失衡，从而导致 “自身免疫性”综合征，继而表现为持续性的神经根性疼痛。这个 在本申请中提出的研究，当与我们以前的 数据，将决定个人角色和集体交互 特异性细胞因子和趋化细胞因子(趋化因子)与细胞转运 在持续性神经根性疼痛的病因学上。中心假设将是 使用我们实验室的既定方法进行测试，以调查 以下是具体目标： 1.评估趋化因子在持续性神经根性疼痛病因中的作用 采用慢性腰神经根病(C-LR)啮齿动物模型。 2.继续处理损伤部位与DRG的关系的重要性 为痛苦世代干杯。 3.确定细胞是否从外周进入中枢神经 系统对导致持续性腰神经根损伤的反应 神经根性疼痛。 4.评估根部机械伤害与化学伤害的贡献 炎性成分在神经根性疼痛中的产生。 5.确定选择性和全局性免疫抑制治疗对 改变感觉加工和中枢炎症反应的可能性 卡斯卡德。 完成后，该项目将提供：体内动力学的信息 脊髓促炎症细胞因子和趋化因子的表达和产生 啮齿动物神经根病模型；指导和支持新的 急性和慢性下腰痛的药物治疗；对 神经根损伤的神经免疫反应与神经损伤的关系 腰背痛的临床现象；指导未来研究的初步数据 评估中枢神经免疫激活在低血压病因中的影响 神经根病引起的背痛；病因鉴别的新信息 背根神经节中央或周围神经损伤之间(a 临床相关的解剖位置)。这一新知识将指导 开发新的、非成瘾的预防疗法和治疗方法 慢性腰背痛。

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.