PROPOFOL AND BARBITURATE DEPRESSION OF SPINAL NOCICEPTIVE NEUROTRANSMISSION
PROPOFOL AND BARBITURATE DEPRESSION OF SPINAL NOCICEPTIVE NEUROTRANSMISSION
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DOI：
10.1097/00000542-199212000-00016
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发表时间：
1992-12-01
期刊：
影响因子：
8.8
通讯作者：
KENDIG, JJ
中科院分区：
文献类型：
--
作者：
JEWETT, BA;GIBBS, LM;KENDIG, JJ
巴比妥类药物通常被描述为非镇痛剂，甚至是痛觉过敏剂;较新的静脉麻醉剂丙泊酚被认为是非镇痛剂。异丙酚和巴比妥类药物都占据GABA（A）受体上的位点。本研究旨在比较异丙酚和巴比妥类药物对新生大鼠脊髓伤害性相关神经传递的影响，寻找可能的痛觉过敏作用，并确定GABA（A）受体介导的异丙酚抑制伤害性神经传递的程度。在离体新生大鼠（1-5日龄）灌流脊髓中记录了电刺激背根引起的单突触反射、慢腹根电位（slow VRP）和背根电位（dorsal root potential，DRP）。慢VRP和DRP与伤害性感受有关。异丙酚（0.5-10 μ M）、戊巴比妥（1-10 μ M）和硫喷妥钠（1-10 μ M）可逆地抑制慢VRP。剂量-反应曲线在此范围内呈双相线性。单突触反射不受影响。GABA（A）激动剂蝇蕈醇（0.2-1 μ m）也抑制慢VRP。GABA（A）拮抗剂荷包牡丹碱（1 μ M）可拮抗异丙酚和巴比妥酸盐对VRP的缓慢抑制作用。异丙酚抑制直接应用P物质诱发的反应。DRP是一种GABA（A）介导的初级传入神经末梢去极化，降低伤害性输入的有效性。异丙酚和硫喷妥钠增加电诱发的DRP幅度，并增加应用蝇蕈醇诱发的DRP。因此，丙泊酚和巴比妥类药物都抑制了伤害性相关的慢VRP，并增强了抗伤害性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。丙泊酚和巴比妥类药物的作用至少部分可以通过增强通过与GABA（A）受体相关的通道的传输来解释。结果与最近的证据雅阁，即两种类型的药物在脊髓水平发挥镇痛作用。然而，抗伤害性和全身麻醉剂浓度范围之间的重叠可能导致这些药物在全身给药时“非镇痛”的感觉。
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 GABA(A) 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 GABA(A) 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 muM), pentobarbital (1-10 mum), and thiopental (1-10 mum) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABA(A) agonist muscimol (0.2-1 mum) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABA(A) antagonist bicuculline (1 muM). Propofol depressed the response evoked by direct application of substance P. The DRP is a GABA(A)-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 GABA(A) 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.