Program Director/Principal Investigator (Last, First, Middle): Detloff, Megan Ryan PROJECT SUMMARY Spinal cord injury (SCI) impairs sensory transmission leads to chronic, debilitating neuropathic pain. Chronic pain afflicts over 100 million Americans and creates an enormous burden on US health care systems, costing over half a trillion dollars annually according to a recent report from the Institute of Medicine. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. After SCI, rehabilitative locomotor training is widely used in the clinical SCI population with its primary goal to promote motor recovery after SCI. In the lab, we have shown the timing of exercise is critical to meaningful sensory recovery. Early administration of a sustained locomotor exercise program in spinal cord injured rats prevents the development of neuropathic pain, while delaying similar locomotor training until pain was established was ineffective at ameliorating it. The time elapsed since the injury occurred also indicates the degree of inflammation in the dorsal horn. We have previously shown that chronic SCI and the development of neuropathic pain correspond with robust increases in microglial activation and the levels of pro-inflammatory cytokines. This proposal seeks to lengthen the therapeutic window where rehabilitative exercise can successfully suppress neuropathic pain by pharmacologically reducing inflammation in dorsal root ganglia. We will administer a pharmacologic agent to dampen injury-induced inflammation acutely after SCI prior to and/or at the same time as exercise initiation after spinal cord injury. This will determine whether inflammation must be reduced prior to the initiation of exercise to suppress pain development or if it is sufficient to modulate inflammation at the time exercise is initiated. We will measure changes in the electrophysiological properties of nociceptors related to the extrinsic inflammatory environment in the DRG after SCI in the presence or absence of exercise as a treatment. Information garnered from these experiments would guide future efforts to optimize the treatment of chronic SCI-induced pain by exercise. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page
Detloff, Megan Ryan PROJECT NARRATIVE Rehabilitative exercise can prevent neuropathic pain development when initiated early after spinal cord injury; whereas, delaying exercise intervention until chronic time points can exacerbate pain. This proposal aims to examine the effects of exercise on nociceptor excitiability and the inflammatory environment of the dorsal root ganglia where nociceptors reside. Understanding these interactions will give us a better understanding of the underlying neurobiology to improve the overall management of chronic neuropathic pain, and prevention of development of chronic pain. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page
| Krisa, Laura; Runyen, Madeline; Detloff, Megan Ryan (2018) Translational Challenges of Rat Models of Upper Extremity Dysfunction After Spinal Cord Injury. Top Spinal Cord Inj Rehabil 24:195-205 |
| Chhaya, Soha J; Quiros-Molina, Daniel; Tamashiro-Orrego, Alessandra D et al. (2018) Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury. J Neurotrauma : |
