| dc.description.abstract | Spinal cord injury (SCI) is a traumatic, life-altering injury that results in permanent neurological dysfunction, including chronic neuropathic pain. The mechanisms of SCI-associated pain are incompletely understood, although the numbers of SCI clinical trials testing therapeutic interventions are growing annually. In this dissertation, I will first explore the anatomical mechanisms of SCI pain, then describe a systematic analysis of the current state of SCI clinical trials.
To better understand the anatomical basis of SCI-associated neuropathic pain, specifically mechanical allodynia, we utilized a mouse cervical hemi-contusion model of SCI. We predicted that variability in lesion parameters might explain why some, but not all, experimental animals develop mechanical sensitivity after SCI. We found that 35% of animals exhibiting mechanical sensitivity had significantly increased dorsal horn neuronal sparing and that their tissue displacement at the time of impact was significantly lower. However, we observed no significant differences in dorsal horn nociceptive fiber density. Together, our data indicate that lesion size negatively correlates with the manifestation of at-level mechanical sensitivity and suggests that sparing of dorsal horn neurons may be required for the development of neuropathic pain.
In parallel to the large body of research characterizing pathophysiological mechanisms of SCI, candidate therapeutics continue to be evaluated in SCI clinical trials. Despite this, there is no comprehensive resource making SCI clinical trial information accessible to the lay public. Therefore, we performed a systematic analysis of all the clinical trials registered in the U.S. National Library of Medicine
(ClinicalTrials.gov) focused on improving outcomes after SCI. We annotated and categorized each trial according to the types of interventions tested and the outcome measures assessed. We observed that most trials have low enrollment and test single interventions. Commonly-used interventions include rehab/training/exercise and neuromodulation, and common outcomes focus on improving motor functions. Furthermore, we identify gaps in clinical trial reporting. Together, our work provides a comprehensive glimpse into the past, present, and future of SCI clinical trials, and suggests areas for improvement in clinical trial reporting. | |
