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ASAP Research Grant Recipient: Mary Eaton, PhD, University of Miami School of Medicine, Miami, FL

Project Title: Pre-Clinical Development of GABA cell therapy for chronic pain after SCI

Dates: October 1, 2004 September 30, 2005

Grant Amount: $50,000

Chronic pain is a significant complication affecting most patients who develop syringomyelia. Presently, there are no effective long-term treatments for this condition and therefore efforts are needed to develop and test novel therapeutic interventions. To this end, we will evaluate the effects of transplants of human cell lines that secrete various pain-relieving agents on spontaneous and evoked pain related behaviors in a recently developed model of spinal cord injury (SCI) and syringomyelia. This animal model utilizes intraspinal microinjections of the AMPA/metabotropic glutamate receptor agonist quisqualic acid (QUIS). The toxic properties of QUIS are believed to initiate a central injury cascade that results in neuronal death and the pathogenesis of cavitary lesions within the cord. These findings are similar to those observed in human syringomyelia. QUIS injections also lead to the onset of pain related behaviors, including a hypersensitivity to mechanical and thermal stimuli, especially below the spinal injection site. Collectively, the pathological, behavioral, and physiological changes following QUIS induced injury parallel the clinical profile observed in patients experiencing abnormal sensations, including pain, following SCI and syringomyelia. Using the QUIS model of SCI, we propose to evaluate he effects of transplants of human GABA-secreting cells isolated from a human neuronal cell line. GABA is a normal substance released in the cord that helps dampen pain sensations, but is likely lost or present in reduced amounts following SCI and with syringomyelia.

As a means to ameliorate these problems in humans, we propose to (1) create a perpetual human neural cell line that synthesizes and secretes GABA, characterize these cells in vitro, and (s) test the ability of subarachnoid grafts, near the lumbar cord, of these human GABAergic cells to reduce chronic pain in a rat model of excitotoxic SCI. Furthermore, we plan to develop and eventually test GABA cell therapy (with these human GABA-secreting cells) in human patients with chronic pain after SCI and syringomyelia.