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ANESTHETIC PHARMACOLOGY

Propofol Produces Immobility via Action in the Ventral Horn of the Spinal Cord by a GABAergic Mechanism

Gudrun Kungys, MD^*, JongBun Kim, MD, PhD^*, Steven L. Jinks, MD^*, Richard J. Atherley, BS^*, and Joseph F. Antognini, MD^*

From the *Department of Anesthesiology and Pain Medicine and Section of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, California; and Department of Anesthesia and Pain Medicine, Catholic University of Korea, Seoul, Korea.

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

BACKGROUND: We investigated the actions of propofol and isoflurane on nociceptive responses of neurons in the spinal cord.

METHODS: We determined nociceptive responses of lumbar neurons in the dorsal horn (<1200 µm) and ventral horn (>1200 µm) of decerebrate rats before and during propofol (1 effective dose, ED₅₀) or isoflurane (1 minimum alveolar concentration) anesthesia. During recording of ventral horn neurons, we administered picrotoxin by infusion to determine whether isoflurane and propofol differed in their effects at the aminobutyric acid (GABA) Type A receptors. We also determined whether decerebration altered propofol requirements to produce immobility.

RESULTS: Decerebration did not affect propofol requirements. The ED₅₀ for propofol was 497 ± 58 µg · kg^–1 · min^–1 in intact rats and 420 ± 65 µg · kg^–1 · min^–1 in decerebrated rats (P > 0.05), with corresponding propofol blood concentrations of 8.1 ± 1.1 µg/mL and 7.3 ± 1.1 µg/mL, respectively (P > 0.05). Propofol did not significantly depress dorsal horn neurons, but isoflurane depressed the responses to 56% of control (P < 0.05). Propofol depressed ventral horn neurons to 47% of control, whereas isoflurane depressed ventral horn neurons to 20% of control. Picrotoxin significantly reversed the depressant effect of propofol on ventral horn neuronal responses (79% of control, not significantly different from control). Pic- rotoxin, however, had no effect on isoflurane's depression of ventral horn neuronal responses (26% of control).

CONCLUSIONS: Propofol acts in the spinal cord to produce immobility. This depressive effect occurs in the ventral horn and is mediated mainly by GABA_A receptors. Isoflurane also depresses neurons in the ventral horn; however, isoflurane actions at the GABA_A receptor are either weak or overridden by other effects in the ventral horn.