Propofol and Barbiturate Depression of Spinal Nociceptive Neurotransmission

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Abstract
Barbiturates are often described as non-analgesic or even hyperalgesic agents; the newer intravenous anesthetic agent propofol is said to be non-analgesic. Both propofol and barbiturates occupy sites on the GABAA receptor. The present study was designed to compare the effects of propofol and barbiturates on nociceptiverelated neurotransmission in neonatal rat spinal cord; to search for actions that might be hyperalgesic; and to determine the extent to which propofol depression of nociceptive neurotransmission is mediated by GABAA receptors. The monosynaptic reflex, a slow ventral root potential (slow VRP) and the dorsal root potential (DRP) were recorded from isolated neonatal (1–5 days old) superfused rat spinal cords in response to electrical stimulation of a lumbar dorsal root. The slow VRP and the DRP are related to nociception. Propofol (0.5–10 µM), pentobarbital (1–10 µM), and thiopental (1–10 µM) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABAA aganist muscimol (0.2–1 µM) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABAA antagonist bicuculline (1 µM). Propofol depressed the response evoked by direct application of substance P. The DRP is a GABAA-mediated depolarization of primary afferent nerve terminals that diminishes the effectiveness of nociceptive input. Propofol and thiopental increased electrically evoked DRP amplitude and increased the DRP evoked by application of muscimol. Both propofol and barbiturates thus depressed the nociceptive-related slow VRP and enhanced the antinociceptive DRP; their effective concentrations are at or close to the general anesthetic range for these agents. No anti-analgesic or hyperalgesic effect was observed. Propofol and barbiturate actions could be accounted for at least in part by enhancement of transmission through channels linked to GABAA receptors. The results are in accord with recent evidence that both types of agent exert analgesic effects at the spinal level. However, the overlap between antinociceptive and general anesthetic concentration ranges may contribute to the perception that these agents are “non-analgesic” when administered systemically.

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