The long term goal of our research efforts is to elucidate the interactive contributions of the spinal cord and brain to anesthetic efficacy. Recent data suggest that -isoflurane action in the spinal cord suppresses movement responses to noxious stimuli. Isoflurane (ISO) and halothane (HAL), between 0.6 and 0.9 MAC, depress the number of movements (with less effect on the force of the movements) that occur during and after supramaximal noxious stimulation, and at the 0.9 to 1.1 MAC transition, decrease the number of movements and the force of the movements. It is unclear, however, how specific sites within the central nervous system participate in these anesthetic effects. Possible spinal and supraspinal sites include the dorsal horn, central pattern generators, ON- and OFF-cells of the rostralventral medulla (RVM) and cerebral cortex.
The specific aims of this proposal are to determine 1) anesthetic effects on ON/OFF cells and dorsal horn cells (wide dynamic-range and nociceptive specific), and how these effects correlate with the movement pattern; 2) whether decerebration, dorsolateral funiculus (DLF) lesions and reversible cooling block of the cervical spinal cord alters the movement pattern arising from supramaximal stimulation by eliminating any descending influences; 3) anesthetic effects on central pattern generators. We hypothesize that 1) ON/OFF and dorsal horn cell activity is correlated with movement at low but not moderate ISO and HAL concentrations; 2) DLF lesions (by severing communication between the RVM and spinal dorsal horn cells), spinal cord cooling (reversible spinalization) and pre-collicular decerebration will depress the movement pattern at low ISO and HAL concentrations; 3) ISO and HAL will disrupt central pattern generators at clinically relevant concentrations. Understanding the brain/spinal cord relationship vis-a-vis anesthetic action will aid elucidation of the relationship among critical end-points of anesthesia (amnesia, unconsciousness, immobility in response to noxious stimulation), will guide further research into anesthetic mechanisms, and will lead to site-specific anesthetics.
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