Effect of oral ketamine on secondary hyperalgesia, thermal and mechanical pain thresholds, and sedation in humans

Background and Objectives: Ketamine is an N-methyl-D-aspartate (NMDA) recep tor antagonist, and has been proven effective in alleviating secondary hype ralgesia in human subjects when injected intravenously. After oral ingestio n, 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 volun teer received the following treatment regimen, in randomized, double-blind, 3-way cross-over fashion: (A) placebo; (B) ketamine, 0.5 mg/kg; and (C) ke tamine, 1.0 mg/kg. Standardized tissue injury was induced after study medic ation by heating the right calf with a rectangular thermode. The temperatur e was 47 degrees C, and heating time was 7 minutes. The following parameter s were investigated: Pain during induction of the burn injury; heat-pain de tection 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 phalan x 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 obser ved. Conclusion: Oral ketamine 0.5 or 1.0 mg/kg has no effect on secondary hyper algesia or thermal or mechanical pain thresholds in human volunteers.