In a clinical model of dental pain, the analgesic efficacy of local morphine treatment was examined under three different conditions. Patients undergoing dental surgery were randomly assigned to an injection of local anesthetic (articaine) plus 1 mg morphine either into inflamed (n = 14; trial 1) or non-inflamed (n = 24; trial 2) submucous tissue or perineurally n = 19; trial 3). Patients in the control group for each condition (n = 13, trial 1; n = 26, trial 2; n = 16, trial 3) received articaine plus saline. Postoperative pain intensity was assessed by the visual analog scale (VAS) and numeric rating scale (NRS) at 0, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h. In addition, patients recorded the occurrence of side effects and the supplemental consumption of diclofenac. Immediately after the operation, pain scores were reduced to a similar extent in all groups, most likely due to the local anesthetic effect. Thereafter, pain scores and supplemental consumption of diclofenac were significantly lower in patients receiving 1 mg morphine into inflamed submucous tissue than in the control group for up to 24 h. Patients receiving 1 mg morphine into non-inflamed tissue or perineurally did not show any further reduction in pain scores compared to each control group. Our results show in patients undergoing dental surgery that injection of 1 mg of morphine into inflamed tissue results in significant and prolonged postoperative analgesia, whereas administration into non-inflamed tissue or perineurally is not effective. Thus, consistent with experimental studies, the requirement of an inflammatory process for the occurrence of peripheral opioid effects is also found in the clinical setting.

The recent identification of opioid receptors on peripheral nerve endings of primary afferent neurons and the expression of their mRNA in dorsal root ganglia support earlier experimental data about peripheral analgesic effects of locally applied opioids. These effects are most prominent under localized inflammatory conditions. The clinical use of such peripheral analgesic effects of opioids was soon investigated in numerous controlled clinical trials. The majority of these have tested the local, intraarticular administration of morphine in knee surgery and have demonstrated potent and long-lasting postoperative analgesia. As the direct application of morphine into the pain-generating site of injury and inflammation appears most promising, we examined direct morphine infiltration of the surgical site in a unique clinical model of inflammatory tooth pain. Forty-four patients undergoing dental surgery entered into this prospective, randomized, double-blind study. Before surgery they received, together with a standard local anesthetic solution (articaine plus epinephrine) a submucous injection of either 1 mg of morphine (group A) or saline (group B). Postoperative pain intensity was assessed using the visual analog scale (VAS) and numeric rating scale (NRS) at 2, 4, 6, 8, 10, 12, 16, 20 and 24 h after surgery. In addition, patients recorded the occurrence of side effects and the supplemental consumption of diclofenac tablets. Results of 27 patients were analyzed (group A: n=14, group B: n=13). Pain scores which were moderate to severe preoperatively were reduced to a similar extent in both groups up to 8 h postoperatively. Thereafter, pain scores in group A were significantly lower than those in group B for up to 24 h, demonstrating the analgesic efficacy of additional morphine. The time to first analgesic intake and the total amount of supplemental diclofenac were less in group A than in group B. No serious side effects were reported. Our results show that 1 mg of morphine added to a local anesthetic for dental surgery results in significant improvement of postoperative analgesia. Since the majority of dental surgeries is accompanied with an inflammatory reaction, supplemental morphine may be of benefit for the relief of postoperative dental pain.