Local Tissue Biomechanics in Low Back & Radicular Pain

描述（由申请人提供）：本申请旨在测试 关于腰痛的假设，同时也增加了候选人？的技能 在疼痛和神经生理学研究中。作为一名独立研究员，她 提出了一个计划，将有助于过渡到一个独立的研究人员， 结合重点研究和职业发展活动。她 长期的职业目标是发展独立的研究计划 研究疼痛的颈部损伤生物力学实现这一目标的近期目标 在此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腰痛直接相关的研究。 在德利奥博士的指导下，她建议将这些活动 她的训练和研究。达特茅斯据说是一个理想的环境， 是因为德利奥医生吗在疼痛领域的领导地位， 作为一个整体的机构，麻醉学， 脊柱中心和塞耶工程学院。拟议研究 结合生物力学和疼痛的神经免疫学方面来测试 腰椎放射性病变依赖于局部神经根的中心假说 变形和中枢神经可塑性，这是直接影响的 初始组织变形幅度。而低背和 神经根疼痛被认为涉及机械成分， 对神经组织的局部机械反应的不完全理解， 这些疾病。这项工作将研究神经炎症 脊髓致敏机制的生物工程分析 组织损伤现有的腰椎放射性病变大鼠模型用于： (1)量化并关联机械和脊髓神经免疫的差异， 对非炎性和炎性压迫损伤的活化反应， (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的神经炎症相关 急性和慢性神经根性疼痛状态，和（4）使用这些数据来开发 疼痛性神经根损伤的基于应变和基于负荷的标准。到 为了实现这一点，体内组织应变将与机械应变相关。 异常性疼痛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.