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ANESTHETIC PHARMACOLOGY

The Excitatory and Inhibitory Effects of Nitrous Oxide on Spinal Neuronal Responses to Noxious Stimulation

Joseph F. Antognini, MD^*, Richard J. Atherley, BS^*, Robert C. Dutton, MD, Michael J. Laster, DVM, Edmond I. Eger, II, MD, and Earl Carstens, PhD

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

Address correspondence to Joseph F. Antognini, MD, Department of Anesthesiology and Pain Medicine, TB-170, University of California, Davis, CA 95616. Address e-mail to jfantognini{at}ucdavis.edu.

BACKGROUND: Because of the logistical obstacles to measurement under hyperbaric conditions, the effect of nitrous oxide (N₂O) alone on spinal neuronal responses has not been tested. We hypothesized that, like other inhaled anesthetics, N₂O would depress spinal neuronal responses to noxious stimulation.

METHODS: The lumbar spinal cord was exposed in rats anesthetized with isoflurane. Mechanically ventilated rats were placed into a hyperbaric chamber and needle electrodes were inserted into the hindpaws. Isoflurane administration was discontinued and anesthesia converted to N₂O by pressurizing the chamber with N₂O. A microelectrode was inserted into the lumbar cord using computer-controlled motors and a hydraulic microdrive. Neuronal responses to electrical stimulation of the hindpaw were sought at 1.5, 2, and 2.5 atm N₂O (0.8–1.3 minimum alveolar concentration).

RESULTS: Increasing N₂O partial pressures variably affected neuronal responses to a 2 s 100-Hz electrical stimulus. Neuronal depth and neuronal response were correlated, with superficial neurons tending to be facilitated, while deeper neurons were depressed; (overall responses were 1331 ± 408, 1594 ± 383, and 1578 ± 500 impulses/min at 1.5, 2, and 2.5 atm N₂O, respectively; mean, standard error). N₂O did not affect neuronal responses to a repetitive "windup" stimulus. Infusion of the N-methyl-d-aspartate blocker MK-801 into separate rats increased the neuronal response to the 100-Hz stimulus (from 781 ± 216 to 1352 ± 269 impulses/min, P < 0.05).

CONCLUSIONS: N₂O facilitated superficial spinal neuronal responses to noxious stimulation while depressing deeper neurons. These results suggest that anesthetic partial pressures of N₂O have divergent effects on spinal neuronal responses to noxious stimulation, the specific responses depending on the depth of the spinal neurons.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999