: 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.
