Peripheral morphine analgesia in dental surgery

Abstract

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.

Characterization of μ Opioid Receptor Binding and G Protein Coupling in Rat Hypothalamus, Spinal Cord, and Primary Afferent Neurons during Inflammatory Pain

“…The peripheral analgesic effects of opioids are elicited by activation of MOP receptor on primary afferent neurons (DRG). This is best described under local inflammatory conditions and has been shown in clinical (Likar et al, 1998) and experimental (Stein et al, 1989) studies. Intrathecal administration of opioids is widely used in clinical routine and shows significant MOP receptor-mediated analgesic effects at the first synaptic relay in the transmission of nociceptive messages (Julius and Basbaum, 2001).…”

Topical and Peripherally Acting Analgesics

“…Effects are reversible by naloxone, similar in magnitude to conventional local anesthetics, and can last up to 48 h after injection. Peripheral analgesia with morphine also has been observed in dental surgery (Likar et al, 1998(Likar et al, , 2001. Local analgesic actions of morphine also have been examined in arthritis, a condition involving more chronic inflammation.…”

DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic Acid), a Novel, Systemically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: I. In Vitro Pharmacological Characterization and Pharmacokinetic Properties

“…In humans, intra-articular administration of morphine reverses the hyperalgesia associated with osteoarthritis (Stein et al, 1999) or resulting from arthroscopic knee surgery (Kalso et al, 1997). Similar results are seen after submucosal administration of morphine to patients with acute inflammatory tooth pain (Likar et al, 1998). These data suggest that an exogenous, peripherally restricted opioid agonist may provide effective pain relief in inflammation-mediated hyperalgesia without centrally mediated adverse effects.…”