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-TypeA Receptor β3 Subunit

In Brief 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. IMPLICATIONS: Propofol sufficient to produce immobility did not prevent increased activation (c-fos expression) of spinal neurons by intraplantar formalin injection, a finding consistent with propofol lacking analgesic properties. Mice with a mutation of the gamma-aminobutyric acid type A receptor were resistant to propofol anesthesia, supporting the importance of this receptor for propofol’s action.