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ANALGESIA

The Differential Effects of Halothane and Isoflurane on Windup of Dorsal Horn Neurons Selected in Unanesthetized Decerebrated Rats

Toshihiko Mitsuyo, MD, PhD^*, Robert C. Dutton, MD, Joseph F. Antognini, MD, and Earl Carstens, PhD

From the *Department of Anesthesiology and Resuscitology, Ehime University Medical School, Matsuyama, Japan; Department of Anesthesia and Perioperative Care, University of California, San Francisco; and Department of Anesthesiology and Pain Medicine and Section of Neurobiology, Physiology, and Behavior, University of California, Davis.

Address correspondence and reprint requests to Earl Carstens, PhD, Section of Neurobiology, Physiology & Behavior, University of California, Davis, 1 Shields Ave., Davis, CA 95616. Address e-mail to eecarstens{at}ucdavis.edu.

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.

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