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PAIN MEDICINE

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 ß3 Subunit

Austin W. Merrill, BS^*, Linda S. Barter, MVS, Uwe Rudolph, MD, Edmond I. Eger, II, MD, Joseph F. Antognini, MD^*, Mirela Iodi Carstens, BA^*, and E. Carstens, PhD^*

From the *Section of Neurobiology, Physiology and Behavior, Department of Anesthesiology and Pain Medicine, University of California, Davis, California; McLean Hospital, Belmont, Massachusetts; and the Department of Anesthesiology and Perioperative Care, University of California, San Francisco, San Francisco, California.

Address correspondence and reprint requests to Earl E. Carstens, Section of Neurobiology, Physiology & Behavior, University of California, Davis, Davis, California, 95616. E-mail: eecarstens{at}ucdavis.edu.

We investigated whether propofol affected nociceptive behavior and fos-like immunoreactivity (FLI) in the lumbo-sacral spinal cord after intraplantar formalin injection in wild-type (WT) mice and in mutant mice harboring a point mutation of the gamma-aminobutyric acid type _A receptor, which renders them resistant to propofol. Bolus injection of propofol (30 mg/kg IV) in WT mice reduced phase 1 formalin-evoked behavior over the initial 2–3 min but did not alter phase 2 behavior or spinal FLI (64 ± 19 cells/section) compared with WT mice receiving intralipid vehicle plus intraplantar formalin (57 ± 19 cells/section). Most FLI was restricted to superficial dorsal horn laminae ipsilateral to the formalin injection. WT mice receiving a 60-min propofol infusion were anesthetized throughout and did not display nociceptive behavior but had FLI (58 ± 11 cells/section) that did not differ significantly from the other WT groups. Mutant mice receiving bolus injection of propofol (30 mg/kg) and intraplantar formalin were not anesthetized and exhibited nociceptive behavior. The total FLI in the spinal cord was 47 ± 29 cells/section. These data indicate that although propofol produces anesthesia, it does not prevent the FLI that is associated with nociception, a finding consistent with propofol lacking analgesic properties.

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