Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems
Potentiation by ketamine of fentanyl antinociception. I. An experimental study in rats showing that ketamine administered by non-spinal routes targets spinal cord antinociceptive systems
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DOI：
10.1093/bja/88.5.685
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发表时间：
2002-05-01
影响因子：
9.8
通讯作者：
Goodchild, CS
中科院分区：
文献类型：
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作者：
Nadeson, R;Tucker, A;Goodchild, CS
背景资料。氯胺酮已被发现在动物身上发挥抗伤害性作用，并在人类的亚麻醉剂量下具有止痛作用。本研究旨在探讨脊髓机制在非脊髓注射氯胺酮增强阿片类药物镇痛作用中的作用。在大鼠的急性疼痛模型中测量了伤害性阈值，该模型可以识别脊髓中药物作用所致的抗伤害性效应。绘制氯胺酮和氯胺酮联合Mu阿片类芬太尼抗伤害效应的量效曲线。腹腔注射氯胺酮3.75 mg·kg~(-1)不产生镇静或抗伤害效应，鞘内注射氯胺酮产生剂量依赖的脊髓介导的抗伤害效应。单独注射不产生抗伤害效应的氯胺酮剂量(鞘内25杯和腹膜内3.75 mg/kg)在用伤害性热(甩尾法)评估时显著增加鞘内注射芬太尼所产生的脊髓介导的抗伤害性，而在用伤害性电流(电流阈值测试)评估时则不显著。我们得出结论，即使通过非脊髓给药途径给药，氯胺酮也可以通过脊髓水平的相互作用来增强芬太尼的作用。
Background. Ketamine has been found to exert antinociceptive effects in animals and to be analgesic at subanaesthetic doses in humans. This study was designed to investigate the involvement of spinal cord mechanisms in the potentiation of opioid analgesia by parenteral non-spinal administration of ketamine.Methods. Thresholds for nociception were measured in an acute pain model in rats that allowed identification of antinociceptive effects due to drug action in the spinal cord. Dose-response curves for the antinociceptive effects of ketamine alone and ketamine in conjunction with the mu opioid fentanyl were constructed.Results. Intraperitoneal ketamine up to 3.75 mg kg(-1) caused no sedative or antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally mediated antinociceptive effects. Injections of ketamine doses that caused no antinociceptive effects when given alone (intrathecal 25 mug and intraperitoneal 3.75 mg/kg) significantly increased spinally mediated antinociception produced by intrathecal fentanyl injections when assessed using noxious heat (tail-flick test) but not when assessed by noxious electrical current (electrical current threshold test).Conclusions. We conclude that ketamine can potentiate the effects of fentanyl by an interaction at the level of the spinal cord even when ketamine is given via a non-spinal route of administration.