Opioid Analgesics

The etiology of acute pain following tissue injury is nociceptive input from pain sensing nerve endings magnified by the development of sensitization in the periphery due to the release of inflammatory mediators. Nociceptive input into the nervous system is further augmented by facilitation in the trigeminal ganglion and transmission to the cortex, resulting in the perception of pain. Pain pathways are so robust that they are activated even under general anesthesia unless the nociceptive input is blocked in the periphery with a local anesthetic.^3,4 In the immediate postoperative period, continued peripheral nociceptive input from the site of injury and the development of inflammation leads to hyperalgesia that results in greater clinical pain over the first 24 to 48 hours. Recognition of this provides a rationale for attenuating acute pain and the development of hyperalgesia during the postoperative period with peripherally directed strategies to inhibit these mechanisms.

Administration of an NSAID prior to pain onset in the immediate postoperative period provides adequate time for absorption and distribution prior to the offset of local anesthesia, thereby delaying pain onset and reducing its intensity.^5,6 Combining NSAID administration with use of a long-acting anesthetic produces additive analgesia and reduces side effects when compared with an opioid combination. The contribution of both COX-1 and COX-2 enzymes to pain following tissue injury provides a rationale for suppressing prostaglandin E2 with dual-acting NSAIDs.⁷ These findings provide strong evidence that preventive administration of a traditional NSAID (eg, ibuprofen, ketoprofen) suppresses pain on the day of a surgical procedure and that ongoing by-the-clock administration continues to suppress clinical pain while acute inflammation runs its 2- to 3-day postoperative course.

It is now recognized that acetaminophen inhibits prostaglandin formation, augments the effects of endocannabinoids, and inhibits the effects of TRPA1. Therefore, acetaminophen not only reduces levels of prostaglandin E2 at the site of tissue injury, but also produces analgesic effects in the central nervous system. A well-controlled clinical study in patients undergoing oral surgery demonstrated that combining an NSAID with acetaminophen resulted in additive analgesia that was greater than that of either drug alone or an opioid combination.⁸ Systematic reviews⁹ provide strong evidence that combining an NSAID with acetaminophen produces greater analgesia than traditional opioid combinations and without the high incidence of adverse effects.

Traditional opioid analgesic combinations were developed in an era before the NSAIDs were introduced and usually involved low doses of aspirin (eg, 325 mg) or acetaminophen (300 to 325 mg) combined with opioids such as codeine, oxycodone, or hydrocodone. NSAIDs demonstrate greater pain relief and fewer side effects than opioid analgesic combinations with the added benefit of suppressing edema following a surgical procedure. In addition, prescribing practices are often based on the ‘‘worst-case scenario,' which can result in an abundance of leftover, unconsumed medication available for diversion,¹⁰ contributing to abuse,¹¹ addiction, and overdose deaths.

 Based on the large body of evidence that supports a pain prevention paradigm utilizing the administration of long-acting local anesthetics combined with an NSAID and acetaminophen¹² and the weak evidence supporting the administration of opioid combinations, the use of opioids should be considered a therapeutic option of last resort.

About the Authors

Raymond A. Dionne, DDS, MS, PhD, is a research professor at the Brody School of Medicine at East Carolina University, Greenville, North Carolina, and Sharon M. Gordon, DDS, MPH, PhD, is the dean of the University of Connecticut School of Dental Medicine, Farmington, Connecticut.