Local Tissue Biomechanics in Low Back & Radicular Pain

描述(申请人提供)：本申请旨在测试 关于腰痛的假设，同时也增加了候选人？S的技能？ 在疼痛和神经生理学研究方面。作为一名独立研究员，她 提出了一项有助于向独立研究人员过渡的计划， 将重点研究和职业发展活动结合起来。她 长期的职业目标是发展一个独立的研究项目 研究痛性颈部损伤的生物力学。实现这一目标的近期目标 在该奖项的职业发展计划中提供，其中包括 与神经生物学相关的课程和与下腰痛直接相关的研究。 在德利奥博士的指导下，她提议将这些活动纳入 在她的训练和研究中。达特茅斯据说是一个理想的环境， 这样的活动归功于德利奥？S博士在疼痛领域的领导和 机构作为一个整体在麻醉学、 脊椎中心和塞耶工程学院。拟议的研究 将生物力学和疼痛的神经免疫学结合起来进行测试 腰椎放射性眼病依赖于局部神经根的中心假设 变形和中枢神经可塑性直接受 初始组织变形量。而腰背部和腰部的机制 根性疼痛被认为涉及机械部件，有一种 对神经组织局部力学反应的不完全认识 这些疾病。拟议的工作结合了对神经炎性疾病的研究 脊椎敏化机制的生物工程分析 组织损伤。现有的大鼠腰椎放射眼病模型用于： (1)量化和关联机械神经免疫和脊髓神经免疫的差异 非炎症性和炎症性压迫性侮辱的激活反应， (2)定量评估应用神经根损伤的可重复性；(3) 确定局部组织力学和随后相关的神经炎症 急性和慢性神经根性疼痛状态，以及(4)使用这些数据开发 疼痛神经根损伤的标准包括基于应变和基于负荷的。至 做到这一点，体内的组织应变将与机械相关 痛觉过敏和持续性疼痛的神经免疫介质。

DESCRIPTION (provided by the applicant): This application aims to test hypotheses regarding low back pain while also increasing the candidate?s skills in pain and neurophysiologic research. As an independent researcher, she proposes a plan that will help in the transition to an independent researcher, combining both focused research and career development activities. Her long-term career goal is the development of an independent research program studying painful neck injury biomechanics. Immediate goals for achieving this are provided in a career development plan for this award that include both courses related to neurobiology and research directly related to low back pain. Under the mentorship of Dr. DeLeo, she proposes to incorporate these activities in her training and research. Dartmouth is said to be an ideal environment for such activities due to Dr. DeLeo?s leadership in the pain field and the institution as a whole having much collaboration between Anesthesiology, the Spine Center, and the Thayer School of Engineering. The proposed research incorporates aspects of biomechanics and the neuroimnmunology of pain to test the central hypothesis that lumbar radioculopathy depends on local nerve root deformation and central neuroplasticity that is directly influenced by the initial tissue deformation magnitude. While mechanisms of low back and radicular pain are believed to involve a mechanical component, there is an incomplete understanding of the local mechanical response of neural tissue in these diseases. The proposed work combines studying neuroinflammatory mechanisms leading to spinal sensitization with bioengineering analysis of tissue injury. An existing rat model of lumbar radioculopathy is utilized to: (1) quantify and correlate differences in mechanical and spinal neuroimmune activation responses for non-inflammatory and inflammatory compressive insults, (2) quantitatively assess reproducibility in applying a nerve root injury, (3) determine local tissue mechanics and subsequent neuroinflammation associated with acute and chronic radicular pain states, and (4) use these data to develop both strain-based and load-based criteria for painful nerve root injury. To accomplish this, in vivo tissue strains will be correlated with mechanical allodynia and neuroimmune mediators of persistent pain.