This application is a request for an ADAMHA RSDA level II award. This award is sought to enable: 1) broadening the range of approaches applied to the study of pain and analgesia; 2) broadening the research skills of the candidate; and 3) promoting interdisciplinary interactions between the candidate and other investigators within and without the home department. Studies throughout the period of support are designed to examine the mechanism of transmission of algesic and analgesic information across synapses in the spinal cord. Past NIDA-supported studies in this laboratory have set the stage for electrophysiological studies which address more directly the cellular mechanisms underlying the behavioral observations. This project will examine the spinal function of excitatory amino acids (EAAs) and substance P (SP) in the transmission of pain, and will elucidate antinociceptive mechanisms and assign cellular sites of action to opioid and adrenergic agonists in the spinal cord. The requested support will encourage formation of new collaborations with several new faculty members in the department whose expertise includes cellular electrophysiological, biochemical and molecular biological approaches. Patch clamp recordings from acutely dissociated dorsal horn projection neurons will examine the nature of ion channels affected by these neurotransmitters. Late in the grant period, measurement of intracellular calcium transients using microspectrofluorimetry will extend these results to include levels of calcium accompanying these changes. Binding experiments will test the hypothesis that the adrenergic-opioid synergism observed in earlier studies of rodent spinal cord results from an interaction at the receptor level. The long term product of this award would be a progression from early experiments well within the PI's expertise to other experiments well beyond his documented training. This substantial broadening of experience is consistent with the PI's current level of research activities, which include electrophysiology, biochemistry, image processing and molecular biology. These current activities together with the rich Minnesota research environment actually make completion of most of the above projects highly likely. It is important, however, that the PI have increased pure research time available to make maximum productive use of this research environment; this award would provide that increased research time.
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