Effect of oral ketamine on secondary hyperalgesia, thermal and mechanical pain thresholds, and sedation in humans.
OBJECTIVE
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, and has been proven effective in alleviating secondary hyperalgesia in human subjects when injected intravenously. After oral ingestion, ketamine is metabolized into norketamine, which in vitro possesses NMDA receptor antagonistic effect. The aim of this study was to investigate the effects of oral administration of ketamine on secondary hyperalgesia evoked by standardized tissue injury.


METHODS
Twenty-four male volunteers were included in the study. Each volunteer received the following treatment regimen, in randomized, double-blind, 3-way cross-over fashion: (A) placebo; (B) ketamine, 0.5 mg/kg; and (C) ketamine, 1.0 mg/kg. Standardized tissue injury was induced after study medication by heating the right calf with a rectangular thermode. The temperature was 47 degrees C, and heating time was 7 minutes. The following parameters were investigated: Pain during induction of the burn injury; heat-pain detection thresholds in the injured area and a corresponding noninjured area; secondary hyperalgesia surrounding the injured area on the calf; secondary hyperalgesia induced by heating an area on the thigh with 45 degrees C in 3 minutes; pressure-pain detection thresholds measured on the middle phalanx of the 4th left finger; pain during a 60-second thermal stimulation of 46 degrees C on undamaged skin on the left thigh; and side effects.


RESULTS
Some degree of sedation was observed after oral administration of ketamine. No effects on any of the other investigated parameters were observed.


CONCLUSIONS
Oral ketamine 0.5 or 1.0 mg/kg has no effect on secondary hyperalgesia or thermal or mechanical pain thresholds in human volunteers.
Mikkelsen
S
S
Department of Anesthesiology, Copenhagen University Hospital, Herley, Denmark. mikkelsen@dadlnet.dk
Jørgensen
H
H
Larsen
P S
PS
Brennum
J
J
Dahl
J B
JB
D000284:Administration, Oral; D002056:Burns / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007649:Ketamine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine