title: The differential effects of halothane and isoflurane on windup of dorsal horn neurons selected in unanesthetized decerebrated rats.
abstract: Halothane and isoflurane, in the peri-minimum alveolar anesthetic concentration (MAC) range, exert differential effects on spinal nociceptive neurons, whereby halothane further depresses their responses from 0.8 to 1.2 MAC, whereas isoflurane does not. We presently investigated if these anesthetics differentially affect windup, the progressive increase in neuronal responses to repetitive noxious stimuli, over a broad concentration range from 0 to 1.2 MAC. In decerebrated rats, single-unit recordings were made from dorsal horn neurons exhibiting windup to 20 1-Hz C-fiber strength electrical stimuli. Halothane and isoflurane (0, 0.4, 0.8, and 1.2 MAC) were tested in a counterbalanced crossover protocol. Increasing halothane and isoflurane from 0 to 1.2 MAC progressively suppressed the response to the first stimulus, as well as summed responses to all stimuli (to 34% +/- 8% and 50% +/- 8%, respectively; P < 0.05). Absolute windup (summed response minus 20x the first response) was suppressed by both anesthetics from 0 to 0.8 MAC, with further depression by halothane but not isoflurane at 1.2 MAC. Responses of neurons isolated at 0 MAC were partially, but never totally, depressed at 0.8 MAC. The dose-dependent suppression of windup is consistent with reduced temporal summation of pain. Further depression at 1.2 MAC halothane, but not isoflurane, suggests different sites of immobilizing action for these two anesthetics. Immobility seems to not be mediated by severe anesthetic depression of a subpopulation of nociceptive neurons.
authors.affiliation: Department of Anesthesiology and Resuscitology, Ehime University Medical School, Matsuyama, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Mitsuyo
authors.forename: Robert C
authors.initials: RC
authors.lastname: Dutton
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Antognini
authors.forename: Earl
authors.initials: E
authors.lastname: Carstens
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009619:Nociceptors / Q000473:pathology*; D010146:Pain / Q000188:drug therapy*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane