This is a first NIH grant proposal by a young investigator written in response to the program announcement PA-96-026, Molecular Pharmacology of Anesthetic Action. Its goal is to elucidate the interactive contributions of the spinal cord and brain to anesthetic efficacy. In preceding studies the PI has provided evidence that the spinal cord is the site at which an inhalation agent produces immobility in response to a noxious stimulus, and that cerebral contributions are less important and may even antagonize the spinal actions. The present proposal extends the study of spinal-cerebral interactions to intravenous anesthetic and analgesic agents as well as volatile agents, including isoflurane, nitrous oxide, thiopental, propofol and morphine. In a goat model in which brain and spinal cord (torso) can be independently perfused, the investigator will carry out studies to (1) determine how anesthetic action in the brain influences nociceptive responses in spinal cord and (2) determine how anesthetic action in the spinal cord affects transmission of nociceptive information to the brain. Methods include recording nociceptive responses of single neurons in lumbar dorsal horn, mid-brain reticular formation and thalamus, and changes in cortical EEG evoked by noxious stimulation. Predictions are made about the direction and magnitude of the effects of different agents applied to brain on spinal cord, of different agents applied to torso on dorsal horn cells, and of different agents applied to torso on transmission of nociceptive stimuli to supraspinal areas. Understanding the brain/spinal cord relationship in anesthetic action will contribute to elucidation of the relationship among critical end-points of anesthesia, will guide further research into anesthetic mechanisms, and will lead to site-specific anesthetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM057970-01
Application #
2677487
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Kitt, Cheryl A
Project Start
1998-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Davis
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Andrada, Jason; Livingston, Preetha; Lee, Bong Jae et al. (2012) Propofol and etomidate depress cortical, thalamic, and reticular formation neurons during anesthetic-induced unconsciousness. Anesth Analg 114:661-9
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Barter, L S; Mark, L O; Smith, A C et al. (2007) Isoflurane potency in the northern leopard frog Rana pipiens is similar to that in mammalian species and is unaffected by decerebration. Vet Res Commun 31:757-63
Merrill, Austin W; Barter, Linda S; Rudolph, Uwe et al. (2006) Propofol's effects on nociceptive behavior and spinal c-fos expression after intraplantar formalin injection in mice with a mutation in the gamma-aminobutyric acid-type(A) receptor beta3 subunit. Anesth Analg 103:478-83, table of contents
Orth, Mashawn; Bravo, Emigdio; Barter, Linda et al. (2006) The differential effects of halothane and isoflurane on electroencephalographic responses to electrical microstimulation of the reticular formation. Anesth Analg 102:1709-14

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