Isoflurane depression of spinal nociceptive processing and minimum alveolar anesthetic concentration are not attenuated in mice expressing isoflurane resistant γ-aminobutyric acid type-A receptors

Anesthetics produce immobility and depress spinal nociceptive processing, but the exact sites and mechanisms of anesthetic action are unknown. The gamma-aminobutyric acid type-A (GABA A) receptor is thought to be important to anesthetic action. We studied knock-in mice that had mutations in the alpha1 subunit of the GABA A receptor that imparts resistance to isoflurane in in vitro systems. We determined the isoflurane minimum alveolar concentration (MAC) that produces immobility in 50% of subjects and responses of lumbar neurons (single-unit recordings) to noxious stimulation (5 s pinch) of the hindpaw. Isoflurane MAC did not differ between wild-type (1.1 ± 0.1%) and knock-in (1.1 ± 0.1%) mice. Isoflurane depressed neuronal responses to noxious stimulation (60 s period during and after pinch) similarly in both wild-type and knock-in mice (555 ± 133 and 636 ± 106 impulses/min, respectively, at 0.8 MAC and 374 ± 81 and 409 ± 85 impulses/min at 1.2 MAC). We conclude that isoflurane enhancement of alpha1-containing GABA A receptors is not required to produce immobility or depress spinal nociceptive processing.