Arendt-Nielsen L, Petersen-Felix S, Fischer M, Bak P, Bjerring P, Zbinden A M
Laboratory for Experimental Pain Research, Aalborg University, Denmark.
Anesth Analg. 1995 Jul;81(1):63-8. doi: 10.1097/00000539-199507000-00013.
Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor channel blocker known to inhibit "wind-up" and hence central hyperexcitability of dorsal horn neurons. We sought to assess the effect of ketamine on single and repeated nociceptive stimuli. A placebo-controlled, human (12 volunteers) experimental study was conducted in which several psychophysical (pain detection and tolerance thresholds, magnitude ratings) and electrophysiologic (withdrawal reflex) techniques were used 1) to investigate whether a ketamine (0.5 mg/kg) bolus followed by a 20-min infusion (9 micrograms.kg-1.min-1) inhibits central temporal summation to repeated nociceptive electrical stimuli, and 2) to assess quantitatively the hypoalgesic potency using several experimental nociceptive stimuli (argon laser, pressure, electrical). Facilitation of the withdrawal reflex to and pain rating of repeated electrical stimuli (five pulses at 2 Hz) were inhibited by ketamine. Reflex and pain rating to a single stimulus did not change. The pressure pain detection and tolerance thresholds were increased significantly by ketamine, whereas the laser heat pain and tolerance thresholds remained stable compared with placebo. The stimulus response function showed that ketamine reduced the responses to the highest electrical stimulus intensities (1.4, 1.6, and 1.8 times the reflex threshold). We conclude that ketamine inhibits central temporal summation in humans and has a marked hypoalgesic effect on high intensity nociceptive stimuli.
氯胺酮是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体通道阻滞剂，已知其可抑制“wind-up”，从而抑制背角神经元的中枢性过度兴奋。我们试图评估氯胺酮对单次和重复伤害性刺激的影响。开展了一项安慰剂对照的人体（12名志愿者）实验研究，其中使用了多种心理物理学（疼痛检测和耐受阈值、强度评级）和电生理学（退缩反射）技术：1）研究静脉推注氯胺酮（0.5mg/kg）继以20分钟输注（9μg·kg-1·min-1）是否抑制对重复伤害性电刺激的中枢性时间总和；2）使用多种实验性伤害性刺激（氩激光、压力、电刺激）定量评估镇痛效力。氯胺酮抑制了对重复电刺激（2Hz下五个脉冲）的退缩反射增强及疼痛评级。对单个刺激的反射和疼痛评级未改变。氯胺酮使压力疼痛检测和耐受阈值显著升高，而与安慰剂相比，激光热痛和耐受阈值保持稳定。刺激反应函数表明，氯胺酮降低了对最高电刺激强度（反射阈值的1.4、1.6和1.8倍）的反应。我们得出结论，氯胺酮在人体中抑制中枢性时间总和，并且对高强度伤害性刺激具有显著的镇痛作用。
