Effects of the NMDA receptor antagonist ketamine in electrically induced A delta-fiber pain

Abstract

Both ketamine and pethidine have previously been found to have analgesic effects in experimentally induced C-fiber pain. The aim of the present study was to examine the effects of ketamine and pethidine in A delta-fiber-mediated pain induced by electrical tooth stimulation. In this double-blind crossover study, an upper right central incisor was stimulated by a Bofors electrical stimulator before and after the intravenous administration of drugs. According to a randomized protocol and with a one-week wash-out period, 9 healthy female volunteers were given either racemic ketamine 0.3 mg/kg or pethidine 0.7 mg/kg, and 11 participants were given (R)-ketamine 0.5 mg/kg or (S)-ketamine 0.15 mg/kg. Pain thresholds were registered by an amperemeter on the stimulator. Drug-induced side effects were registered by use of a standardized questionnaire and visual analog scales. Both ketamine and pethidine gave significant but short-lasting increases in pain thresholds compared to no medication. The participants reported more pronounced mental side effects after ketamine injection. A comparison of (R)- and (S)-ketamine revealed no statistical difference in the effect on pain thresholds of the two enantiomers at the present doses, but 7 out of 11 participants reported to have fewer and less pronounced side effects from (R)-ketamine than from (S)-ketamine. Ketamine and pethidine have only a marginal effect on pain thresholds in electrically induced A delta-fiber-mediated tooth pulp pain, in contrast to the analgesic effects previously found in experimental and postoperative C-fiber-mediated pain. The ketamine enantiomers at the doses used in this study showed equal analgesic properties but different side effect profiles.