Propofol Produces Immobility via Action in the Ventral Horn of the Spinal Cord by a GABAergic Mechanism
Year: 2009
Type: article
Abstract: In Brief 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 γ 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 GABAA receptors. Isoflurane also depresses neurons in the ventral horn; however, isoflurane actions at the GABAA receptor are either weak or overridden by other effects in the ventral horn. IMPLICATIONS: Propofol did not depress spinal dorsal horn neurons, which were depressed by isoflurane. Both anesthetics caused greater depression in the ventral horn. Picrotoxin reversed the depressive effect of propofol, but it had little or no effect on isoflurane's depressive action. In addition, decerebration did not alter propofol requirements. These data suggest that propofol produces immobility by a GABAergic action on neurons in the ventral spinal cord.
Source: Anesthesia & Analgesia
Institutions: University of California, Davis, Catholic University of Korea
Language: English
Subfield: Anesthesiology and Pain Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2057227458