Jewett B A, Gibbs L M, Tarasiuk A, Kendig J J
Department of Anesthesia, Stanford University School of Medicine, California.
Anesthesiology. 1992 Dec;77(6):1148-54. doi: 10.1097/00000542-199212000-00016.
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 nociceptive-related 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 microM), pentobarbital (1-10 microM), and thiopental (1-10 microM) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABAA agonist muscimol (0.2-1 microM) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABAA antagonist bicuculline (1 microM). 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. (ABSTRACT TRUNCATED AT 250 WORDS)
巴比妥类药物常被描述为非镇痛剂甚至是痛觉过敏剂；新型静脉麻醉剂丙泊酚据说也无镇痛作用。丙泊酚和巴比妥类药物都占据γ-氨基丁酸A（GABAA）受体上的位点。本研究旨在比较丙泊酚和巴比妥类药物对新生大鼠脊髓中伤害性相关神经传递的影响；寻找可能导致痛觉过敏的作用；并确定丙泊酚对伤害性神经传递的抑制作用在多大程度上是由GABAA受体介导的。在分离的新生（1 - 5日龄）经灌注的大鼠脊髓上，记录单突触反射、慢腹根电位（slow VRP）和背根电位（DRP），以响应腰背部背根的电刺激。慢VRP和DRP与痛觉感受有关。丙泊酚（0.5 - 10微摩尔）、戊巴比妥（1 - 10微摩尔）和硫喷妥钠（1 - 10微摩尔）可逆地抑制慢VRP。在此范围内剂量 - 反应曲线呈单相且线性。单突触反射未受影响。GABAA激动剂蝇蕈醇（0.2 - 1微摩尔）也抑制慢VRP。丙泊酚和巴比妥类药物对慢VRP的抑制作用被GABAA拮抗剂荷包牡丹碱（1微摩尔）拮抗。丙泊酚抑制直接应用P物质所诱发的反应。DRP是GABAA介导的初级传入神经末梢去极化，可降低伤害性输入的有效性。丙泊酚和硫喷妥钠增加电诱发的DRP幅度，并增加应用蝇蕈醇所诱发的DRP。因此，丙泊酚和巴比妥类药物均抑制与伤害性相关的慢VRP并增强抗伤害性DRP；它们的有效浓度处于或接近这些药物的全身麻醉范围。未观察到抗镇痛或痛觉过敏作用。（摘要截断于250字）
