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2002 Director's Summary Synopsis

PRE-CLINICAL TREATMENTS FOR PAIN
Mary J. Eaton, Ph.D. • Martin Oudega, Ph.D.

Miami Project researchers have shown that the transplantation of adrenal medulla chromaffin cells at the surface of the spinal cord can alleviate many symptoms of chronic pain. In experimental models, they have been determining how various approaches exert their analgesic effects. As this promising research continues, they work to understand how we can translate potential therapies into feasible approaches for humans.

Last year, we reported on a procedure that provides an alternate source of chromaffin cells. Instead of taking chromaffin cells directly from the adrenal gland, researchers developed a way to reproduce chromaffin cells in the culture dish. This procedure involves the insertion of a cancer gene into the cell to promote cell duplication. Because of the concern for tumor formation following transplantation, using genetically modified cells in humans raises questions about their feasibility. In the study above, Dr. Eaton tested a technique to remove the cancer gene from the genetically altered chromaffin cells. When she transplanted the disimmortalized cells in experimental models of pain, they were just as effective in changing the response to pain as the chromaffin cells that were not disimmortalized. The results of this study have the potential to make the transplantation of genetically engineered cells safer for humans.

Other Miami Project researchers have evaluated different approaches to delivering analgesic agents in and around the injured spinal cord. Vector-mediated gene transfer may provide an alternative method to reverse chronic pain after SCI. In one study, Drs. Oudega and Eaton used gene vectors to cause over-expression of a neurotrophin (BDNF) which appears to promote recovery of function and affect the animal’s sensitivity to pain. Success with studies such as these will pave the way to translating this new knowledge into treatments for humans.

Synopsis Publications

 Eaton MJ, Herman J-P, Jullien Nicolas, Lopez TL, Martinez M, Huang J (2002) Immortalized chromaffin cells disimmortalized with Cre/lox site-directed recombination for use in cell therapy for pain after partial nerve injury. Exp Neurol 175:49-604.

 Eaton MJ, Blits B, Ruitenberg MJ, Verhaagen J, Oudega M (2002) Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord. Gene Ther. 2002 Oct;9(20):1387-95.

 
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