During my research training and academic career, I have conducted research in several areas in biology and medicine. Since receiving an academic position, I have selected my research objectives based on available opportunities, rather than on true interests. Partly as a consequence, I have not developed the skills and background necessary to be an independent investigator in an important area of research. Now that my previous research efforts have reached completion, I have the opportunity to carefully consider future research directions. I have decided to focus on the pharmacology of pain because this field is of innate interest, important and topical, and relevant to my clinical discipline of anesthesiology. This application requests funds which will enable me to reduce my clinical and institutional responsibilities, allowing me to focus on developing as an independent investigator. This mentored experience will be under the guidance of an outstanding sponsor, Professor Frank Porreca. The proposed research uses the rat L5-L6 spinal nerve root ligation model to test the hypothesis that loss of intrinsic gamma-amino butyric acid (GABA) tone may be responsible, in part, for the allodynia and hyperalgesia observed in some neuropathic pain states. It tests the related hypothesis that spinally administered GABA agonists will be effective allodynia and hyperalgesia, that GABA agonists given at the time of nerve injury will reduce the magnitude of allodynia and hyperalgesia after injury, and that decreased GABA receptor density or function may be responsible, in part, for loss of GABA-mediated inhibitory tone after nerve injury. The proposed research also investigates aspects of the interaction of spinal and supraspinal GABA receptors in regulating the intensity of nociconception after nerve injury. This project has scientific benefit. In addition, it will expose me to a new literature and modern experimental approaches, including the L5-L6 spinal nerve root ligation model, assessment of hyperalgesia and allodynia, radioligand binding techniques, and principles of pharmacological investigation. With Dr. Porreca's guidance regarding career development, this research proposal and development plan will allow me to develop into an independent investigator. This experience is consistent with my long-term career goal: to become an independent investigator in the basic science of pain biology, while looking for ways to bridge the gap between basic research and clinical application.
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