The long-term objectives of this research plan continue to be the development of a concise description of the physiology and pharmacology of sensory neurons, especially those associated with pain, in the dorsal horn of the spinal cord of physiologically intact, awake, drug free, restrained cats. This proposal is unique in that it will involve extracellular recordings from single spinal neurons in intact, awake, animals. This will permit an evaluation of the systems as they normally function without confounding influences of anesthesia, decerebration, or spinal cord transection. WDR (multireceptive) neurons, because of their unique response to both noxious and non-noxious stimuli, have been assigned a central role in many theories of spinal transmission of pain information. In addition, WDR neurons have been identified as sites of action of anesthetic and analgesic drugs. In spite of their prominent role in the pain literature, however, the physiologic significance of WDR neurons is still open to question. Recent results obtained from work funded by this grant have revealed two important findings about WDR neurons in the intact animal. First, the number of WDR neurons encountered in the spinal dorsal horn of intact animals is much less than would be predicted from results obtained form acute studies. Secondly, barbiturate anesthesia appears to unmask WDR response profiles of some spinal dorsal horn neurons. Because of the potentially important role of WDR neurons in our understanding of the neurophysiology and pharmacology of anesthesia and analgesia, it is essential that we have a clear appreciation of the factors that regulate wide dynamic range neuron response properties in physiologically intact, awake, drug free animals. As such, this proposal has, as its specific aims, the following: 1) to determine if unmasking of WDR response profiles is a barbiturate-specific effect or if it can be produced by other general anesthetics; 2) to determine if changes in arousal associated with the transition form the awake to the sleep state produce unmasking of WDR response profiles; 3) to determine if descending inhibition from the locus coeruleus contributes significantly to the masking of WDR response profiles in intact animals; 4) to determine, at the level of the spinal cord, what effect pharmacological blockage of noradrenergic systems has upon the unmasking of WDR response profiles.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Surgery, Anesthesiology and Trauma Study Section (SAT)
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Yale University
Schools of Medicine
New Haven
United States
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