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ANESTHETIC PHARMACOLOGY

Isoflurane Depresses Windup of C Fiber-Evoked Limb Withdrawal with Variable Effects on Nociceptive Lumbar Spinal Neurons in Rats

Steven L. Jinks, PhD^*, Joseph F. Antognini, MD^*,, Robert C. Dutton, MD, Earl Carstens, PhD, and Edmond I Eger, II, MD

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

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

Windup is a progressive increase in responses of nociceptive spinal cord neurons to repeated electrical C fiber stimulation. We hypothesized that isoflurane would depress windup at approximately the minimum alveolar anesthetic concentration (MAC) required to suppress purposeful movement in response to noxious stimulation. We recorded windup responses in single lumbar spinal neurons (n = 17) to a series of 15 repetitive electrical stimuli delivered at 1 Hz to the hindpaw at C fiber strength; hindpaw withdrawal force was simultaneously recorded. The total number of action potentials per 15 stimuli (mean ± SEM as a percentage of each neuron’s maximal response) was 83% ± 5%, 84% ± 5%, 67% ± 7%, and 57% ± 8% at 0.7, 0.9, 1.1, and 1.4 MAC, respectively. The 0.9 and 1.1 MAC values differed significantly from each other, whereas the 0.7 and 0.9 MAC values differed from the 1.4 MAC value (P < 0.05). The reduced firing was attributed to a depression of the initial C fiber-evoked responses in most units, and a reduction in windup slope over the initial 5 stimuli in 6 units. Muscle force was 67%, 11%, and 4% of the 0.7 MAC value at 0.9, 1.1, and 1.4 MAC, respectively. Isoflurane depressed excitability and variably affected windup of lumbar spinal cord neurons, while uniformly depressing windup of limb withdrawals in a concentration-dependent manner.

IMPLICATIONS: Isoflurane may exert part of its antinociceptive action by depressing spinal cord neuronal excitability and windup, an action that might occur at least partly at the N-methyl-D-aspartate receptor.

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