Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery

Forty-eight patients received either naloxone (10 mg), fentanyl (0.1 mg), diazepam (0.3 mg/kg), or saline solution placebo, and then underwent surgical removal of impacted third molars under local anesthesia. Placebo resulted in significantly elevated levels of immunoreactive beta-endorphin (i beta-END), norepinephrine, and anxiety during surgery. Patients receiving naloxone had significantly greater intraoperative i beta-END and pain as compared with those receiving placebo. The naloxone effect on intraoperative pain was a result of a difference in perceived unpleasantness. Both the fentanyl and diazepam groups had significantly lower intraoperative i beta-END and anxiety levels as compared with the placebo group. Norepinephrine levels increased significantly in response to surgical stress in all groups except the diazepam group. Postoperative circulating levels of i beta-END and norepinephrine and pain increased significantly from the 1 to 3-hour postoperative period for all groups, with the exception of stable norepinephrine levels observed in patients receiving diazepam. Results indicate that opiate antagonists stimulate and agonists suppress the release of i beta-END, possibly by affecting the patient's perceived level of pain and anxiety. In addition, the association of intraoperative hyperalgesia with naloxone predosing suggests that endogenous opioid peptides inhibit the perception of intraoperative pain even in the presence of concurrent local anesthesia.