Neuropeptidergic Inhibition of Spinal Pain Transmission

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DESCRIPTION (provided by applicant): The candidate for an Independent Scientist Award (K02) seeks five years of salary support to provide release time to study the role of neuropeptides in mediating inflammatory and neuropathic pain. His integrative approach includes pharmacologic, behavioral and molecular studies. The candidate obtained a Ph.D. at UCSD, worked with Allan Basbaum at UCSF, and is now an Associate Professor of Pharmacology at Tulane University. He has published 28 original articles (25 as first/last author) plus 7 invited reviews and received NRSA, FIRST (R29), R21 and R01 grants to study pain and analgesia. His broad career goals include: 1. Extension of his current R01 into a well-conceived, long-term research program that yields a new pharmacotherapy for chronic pain (e.g. an NPY receptor agonist); 2. Continued interactions with mentors that will foster his deeper understanding of the physiological, cellular and biochemical mechanisms of chronic pain and its inhibition by neuropeptides; and 3. Continued collaborations and training in the utilization of molecular biological, viral transfection, and conditional transgenic mouse technologies so as to develop precise and targeted approaches to important questions in chronic pain research. Tulane remains rich in educational opportunities for intellectual growth and independence, and provides outstanding resources to Dr. Taylor including laboratory space, equipment, behavioral suites in the vivarium, and internal research funding. Tulane considers Dr. Taylor to be an integral part of its strong commitment to research, and granted him early tenure in 2004. Contingent upon K02 funding, the institution provides assurances that 85% of Dr.Taylor's time will be set aside for research and career development activities. The Research Plan focuses on the overall hypothesis that inflammatory or sensory nerve injury decreases presynaptic and postsynaptic elements of NPY signaling at the dorsal horn, thereby facilitating pronociceptive neurotransmission, and ultimately increasing allodynia and hyperalgesia. Aim #1 will determine the contribution of Y1 or Y2 receptors to the actions of NPY using new receptor subtype- selective antagonists, and deletion mutant mice. Aim #2 will correlate injury-induced changes in behavior with NPY release and Y1 receptor expression. Aim #3 will use microdialysis and immunohistochemistry to determine whether NPY inhibits substance P release and dorsal horn nociresponsive neurons.