Date of Project
School of Movement and Rehabilitation Sciences
Dr. Sonja Bareiss
Chronic neuropathic pain is a very common consequence following spinal cord injury (SCI) and poses significant clinical challenge. Current treatments are largely ineffective and as a result, patients are often left with debilitating pain at and below the level of the spinal cord injury. After spinal injury, a cascade of events occurs within the nervous system. One important aspect of this cascade for investigation is the anatomical changes that occur post-SCI. There is evidence of maladaptive sprouting/growth in sensory nerve fibers that is thought to play a role in the development and amplification of pain signals. Sprouting of primary afferents in the cord, mediated by the dorsal root ganglia (DRG) may contribute to the sensory issues that patients experience after injury. The signaling cascade involving the protein glycogen synthase kinase- 3 beta (GSK-3β) may be important in this maladaptive growth. GSK-3β is highly expressed in the nervous system and is a known regulator of neurite growth through its interactions with cytoskeletal molecules. Recent evidence has shown a potential role for GSK-3β in contributing to pain post-SCI. The purpose of this study was to characterize alterations in GSK-3β in sensory processing regions of the spinal cord dorsal horn and DRG and correlate these expression changes with the presence of pain in a rat model of SCI. Long-Evans rats underwent intramedullary injection of quisqualic acid (QUIS) of saline (sham control) and were allowed to survive for 1 or 22 days. Animals in the 22-day group were examined daily for onset and severity of at-level pain related behaviors termed “overgrooming.” Spinal cord and DRG just below the level of injury were analyzed for alterations in GSK-3β activity. Immunohistochemical staining shows early and persistent changes in GSK-3β expression in the spinal cord dorsal horn and DRG. These findings further support a role for GSK-3β signaling in sensory afferent plasticity and provide insight into a molecular target in SCI-induced pain.
Ernst, Emily, "A Potential Role of GSK-3beta in the Development of Pain Post-Spinal Cord Injury" (2023). Undergraduate Theses. 128.