The goal of this research plan is to examine the effects of inhalation anesthetic agents on sensory processing in the spinal dorsal horn of physiologically intact, awake, drug-free animals. The proposal is unique in that it will employ extracellular recordings from neurons in intact, awake animals allowing evaluation of systems as they function normally without confounding influences of anesthesia, decerebration or spinal cord transection. We have recently demonstrated a profound effect of pentobarbital and propofol on spinal dorsal horn neurons but an apparent lack of similar effects by ketamine. An understanding of the mode of action of general anesthetics is an elusive but important goal. By documenting specific effects of anesthetic agents on sensory neurons in the spinal dorsal horn, we hope eventually to be able to define the pharmacology responsible for the observed changes- knowledge that may provide further insights into the mechanisms of action of general anesthetics. While recording extracellular activity from single spinal dorsal horn neurons in physiologically intact, awake, drug-free animals, we propose to determine baseline neuronal responses to noxious and non-noxious somatic stimuli induce anesthesia with the short-acting intravenous anesthetic propofol and maintain anesthesia with varying concentrations of halothane, enflurane, isoflurane and nitrous oxide. At a time when propofol effects have dissipated and an equilibrium state is established with the inhalation agent, we will evaluate the neuronal response to the same stimuli used in baseline studies. These results, when combined with data from intravenously administered anesthetics will help to define the effect of general anesthetics on sensory processing in spinal dorsal horn neurons and may provide insight into the mechanisms of general anesthesia.
