The Effect of N-Methyl-D-aspartate Antagonist (Ketamine) on Single and Repeated Nociceptive Stimuli: A Placebo-Controlled Experimental Human Study

• Published in: Anesthesia and analgesia Vol. 81; no. 1; pp. 63 - 68
• Main Authors: Arendt-Nielsen, L., Petersen-Felix, S., Fischer, M., Bak, P., Bjerring, P., Zbinden, A. M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01-07-1995; Lippincott
• Subjects: Analgesics; Analgesics - pharmacology; Biological and medical sciences; Cross-Over Studies; Double-Blind Method; Electric Stimulation; Electromyography; Evoked Potentials; Humans; Ketamine - adverse effects; Ketamine - pharmacology; Lasers; Medical sciences; N-Methylaspartate - antagonists & inhibitors; Neuropharmacology; Nociceptors - drug effects; Pain - physiopathology; Pain - prevention & control; Pain Threshold - drug effects; Pharmacology. Drug treatments; Physical Stimulation; Placebos; Pressure; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Reflex - drug effects; Sural Nerve - physiopathology; Human; Nociception; Analgesic; Antagonist; Mechanism of action; NMDA receptor
• ISSN: 0003-2999; 1526-7598
• 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 micro gram centered dot kg centered dot min) 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.(Anesth Analg 1995;81:63-8)