BENZODIAZEPINE MEDIATED ANTAGONISM OF OPIOID ANALGESIA

Activation of supraspinal gamma-aminobutyric acid-A (GABA(A)) receptor s is known to result in antagonism of opioid analgesia. Since benzodia zepines enhance the action of GABA at GABA(A) receptors, we hypothesiz ed that administration of these agents for preoperative sedation might antagonize the analgesic effects of opioids administered postoperativ ely. If so, then administration of the benzodiazepine antagonist fluma zenil should enhance postoperative morphine analgesia. In a double-bli nd, placebo-controlled study of patients who received a preoperatively administered benzodiazepine (diazepam) for sedation and a postoperati vely administered opioid (morphine) for analgesia, we investigated opi oid-benzodiazepine interactions affecting postoperative dental pain, W e found that flumazenil significantly enhanced morphine analgesia cons istent with the hypothesis that the preoperatively administered benzod iazepine exerts an ongoing antianalgesic effect. In addition, we follo wed these patients over the first and second postoperative days to det ermine if there were differences between the drug groups in post-disch arge pain, analgesic consumption, or side-effects. Participants receiv ing flumazenil reported significantly less post-discharge nausea and u sed significantly less ibuprofen. Since post-discharge pain levels wer e nor significantly different, these results suggest that the patients receiving flumazenil required less analgesic medication to achieve a comparable level of pain control. In summary, our results indicate tha t the benzodiazepine antagonist flumazenil enhances morphine analgesia and decreases post-discharge side-effects as well as post-discharge n eed for analgesic medication. (C) 1997 International Association for t he Study of Pain.