title: Isoflurane depression of spinal nociceptive processing and minimum alveolar anesthetic concentration are not attenuated in mice expressing isoflurane resistant gamma-aminobutyric acid type-A receptors.
abstract: 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 (GABAA) receptor is thought to be important to anesthetic action. We studied knock-in mice that had mutations in the alpha1 subunit of the GABAA 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 GABAA receptors is not required to produce immobility or depress spinal nociceptive processing.
authors.affiliation: Department of Anesthesiology, The Catholic University of Korea, Seoul, South Korea.
authors.forename: JongBun
authors.initials: J
authors.lastname: Kim
authors.forename: Richard
authors.initials: R
authors.lastname: Atherley
authors.forename: David F
authors.initials: DF
authors.lastname: Werner
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D013238:Stereotaxic Techniques
chemical_list: D018685:Anesthetics, Inhalation; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D007530:Isoflurane