title: Is a new paradigm needed to explain how inhaled anesthetics produce immobility?
abstract: A paradox arises from present information concerning the mechanism(s) by which inhaled anesthetics produce immobility in the face of noxious stimulation. Several findings, such as additivity, suggest a common site at which inhaled anesthetics act to produce immobility. However, two decades of focused investigation have not identified a ligand- or voltage-gated channel that alone is sufficient to mediate immobility. Indeed, most putative targets provide minimal or no mediation. For example, opioid, 5-HT3, gamma-aminobutyric acid type A and glutamate receptors, and potassium and calcium channels appear to be irrelevant or play only minor roles. Furthermore, no combination of actions on ligand- or voltage-gated channels seems sufficient. A few plausible targets (e.g., sodium channels) merit further study, but there remains the possibility that immobilization results from a nonspecific mechanism.
authors: Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143-0464, USA. egere@anesthesia.ucsf.edu
authors: Edmond I
authors: EI
authors: Eger
authors: Douglas E
authors: DE
authors: Raines
authors: Steven L
authors: SL
authors: Shafer
authors: Hugh C
authors: HC
authors: Hemmings
authors: James M
authors: JM
authors: Sonner
mesh_terms: D000698:Analgesia; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D006801:Humans; D007103:Immobilization; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D008962:Models, Theoretical; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000627:therapeutic use; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D055672:Static Electricity
chemical_list: D018685:Anesthetics, Inhalation; D008024:Ligands; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D044406:Receptors, Serotonin, 5-HT3; D015222:Sodium Channels