INHALATION ANESTHETIC EFFECTS ON THE SPINAL DORSAL HORN

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A long-term goal of our laboratory is to understand how general anesthetics alter sensory processing in the spinal cord. Recent work in our laboratory has revealed anesthetic related changes in the size of peripheral receptive fields and neuronal responses to non-noxious receptive field stimulation. The specific aim of this research project is to use those observed anesthetic effects as a tool to define what transmitter systems are involved in modulation of spinal sensory processing by selected general anesthetic agents. That information will provide a better understanding of the pharmacologic mechanisms by which general anesthetics alter nervous system function. Two separate protocols will be employed to answer the following 4 questions: 1.) What neurotransmitter systems contribute to the ability of halothane to depress receptive field size and neuronal response to receptive field brushing? 2.) What neurotransmitter systems contribute to enflurane's ability to depress receptive field size while at the same time enhancing neuronal response to brushing of the remaining receptive field? 3.) Does the new inhalation anesthetic desflurane differ from halothane and enflurane in its effects on spinal sensory processing? 4.) What neurotransmitter systems contribute to the ability of desflurane to alter spinal sensory processing? Questions 1, 2, and 4 will be answered by studying the effects of systemically and/or spinally administered neurotransmitter receptor agonists and antagonists on halothane, enflurane and desflurane induced alterations in spinal dorsal horn neuronal responses to non-noxious stimulation of peripheral receptive fields in acute rat preparations. Question 3 will be answered by examining the effects of desflurane on spinal dorsal horn neuronal responses to non-noxious and noxious receptive field stimulation in a chronic cat preparation. These studies should define, at the receptor level, systems that contribute to the ability of selected anesthetics to alter spinal sensory processing. While ultimate mechanisms of action are molecular in nature, results from this study will help to define neurotransmitter systems that are likely to be the mechanism by which molecular actions of anesthetics are translated into systemic effects that alter the ability of the nervous system to process sensory information.