May 2017
Volume 38, Issue 5


A Targeted Approach for Managing Nociceptive Orofacial Pain

Mark Donaldson, BSP, ACPR, PHARMD

Oral healthcare professionals (OHCPs) are regularly required to select and prescribe analgesics to treat orofacial pain.1 While pain has both psychological and physiological components, an experience of poorly managed pain can lead patients to postpone or avoid dental treatment, resulting in patients who are even more difficult to treat and less likely to be compliant with prescribed treatments. Appropriately selected medications that reduce orofacial pain improve clinical outcomes, making them an essential part of dental practice.2

In general, orofacial pain results from two pathological processes: (1) tissue injury and inflammation (nociceptive pain); or (2) a primary lesion or dysfunction of the nervous system (neuropathic pain). Determining the underlying pathophysiology, whether it is primarily nociceptive, neuropathic, or a combination of the two, is the first step in the appropriate management of orofacial pain and in the selection of medication(s) whose mechanism(s) of action will specifically target the cause (Figure 1).

While defining the underlying pathophysiology of orofacial pain is straightforward in instances of acute pain, such as a simple toothache or mucosal pain with proximate physical findings (signs of injury, inflammation, and tenderness), the determination is more difficult if the pain is persistent without a clear local cause (eg, neuropathic pain or myofascial pain). This article will focus primarily on the appropriate management of nociceptive orofacial pain.

Pathophysiology of Nociceptive Orofacial Pain

Tissue damage during dental surgery stimulates the release of inflammatory mediators at the site of injury: kinins, histamine, substance P, leukotrienes, and prostaglandins. These mediators initiate and magnify pain impulses, which are transmitted to the central nervous system to generate the perception of pain. Of all of these mediators, prostaglandins are principally important for sensitizing peripheral neurons. Prostaglandins are also synthesized in the higher brain centers and spinal cord in response to pain impulses and amplify pain sensitivity by recruiting additional secondary neurons in response to the primary stimulus.

Aspirin and related nonsteroidal anti-inflammatory drugs (NSAIDs) target the site of tissue damage, along the spinal cord and in the higher brain centers, inhibiting prostaglandin formation by impeding cyclooxygenase (COX) activity. COX mediates the conversion of arachidonic acid to prostaglandins; so inhibiting this enzyme ameliorates the inflammatory triad of pain, inflammation, and fever. Unfortunately, arachidonic acid is also converted to cytoprotective prostaglandins, so aspirin and other NSAIDs can cause adverse effects such as prolonged bleeding, gastroduodenopathies, delayed wound healing,3 and an increased risk of cardiovascular events. A recent meta-analysis, however, demonstrated that patients taking routine NSAIDs for 10 days or less to alleviate pain are not at any increased risk for adverse cardiovascular side effects.4

The cyclooxygenase enzyme has two subtypes: COX-1 and COX-2. COX-1 mediates the synthesis of thromboxane A2, which increases platelet adhesion and degranulation and maintains stomach mucosal integrity and kidney function, while COX-2 plays a major role in mediating inflammation, pain, and fever by promoting the formation of pro-inflammatory prostaglandins. The development of COX-2–specific NSAIDs, such as celecoxib, was intended to target these positive therapeutic effects while avoiding some of the adverse effects of inhibiting the COX-1 subtype.

Pharmacotherapy for Nociceptive Orofacial Pain

The three major etiologies of nociceptive orofacial pain are: musculoskeletal conditions (eg, temporomandibular joint capsulitis, myofascial pain, arthritis); mucosal conditions (eg, lichen planus, ulcers, herpes simplex); and odontogenic conditions (eg, apical periodontitis, pulpitis).1 Except for myofascial pain, these conditions arise from a defined source of tissue injury, inflammation, and nociceptor sensitization. Since pain due to inflammation can also have an underlying infectious etiology, both anti-inflammatory analgesics and antimicrobial agents may be required (Figure 2).

Nociceptive orofacial pain may resolve spontaneously once the underlying cause is treated (eg, inflamed pulp, abscessed gingiva, carious lesion). If it does not, a pharmacologic approach to pain management should be considered.5-8 Current research, evidence and best-practice recommendations support acetaminophen and NSAIDs as the medications of choice to treat nociceptive orofacial pain.6-8 The mechanism of action of all NSAIDs is to inhibit COX enzymes responsible for the formation of prostaglandins that promote pain, inflammation, and fever.9 Some commonly prescribed NSAIDs in the United States are listed in Table 1 through Table 3.10,11

Acetaminophen has a synergistic effect when administered with a NSAID and the combination has repeatedly shown superior analgesic efficacy compared to either drug alone.5,7,8 This therapeutic combination also has a better side-effect profile compared to opioids and no potential for abuse.2,7,8 For example, NSAIDs have been shown to reduce the incidence of postoperative nausea and vomiting by up to 30% compared to narcotics.12 Knowledge and understanding of individual maximum recommended doses is needed, because the most effective dose for the shortest period of time will provide the greatest pain relief balanced against patient safety concerns.2

Unfortunately, a historical though unfounded belief exists that patients with significant orofacial pain should be prescribed opioid-containing analgesics. This misinformation has added to the current “war on drugs.” Studies have shown that opioids are the most prescribed medication of any drug category in the United States, exceeding 250 million prescriptions annually.13 In addition, national surveillance data shows that OHCPs are the one of the leading prescribers of immediate-release opioids behind primary care physicians and, as such, have been identified as having an important role in opioid abuse prevention efforts.14,15 Opioids are frequently prescribed for short-term orofacial pain management associated with dental procedures in emergency and clinical settings despite the fact that they do not target the underlying pathophysiology of orofacial pain and are not anti-inflammatory agents.5-7

OHCPs should remember the “2-4-24” mnemonic as the postoperative prescription of choice for acute nociceptive orofacial pain (two drugs, four doses, for 24 hours): a combination of ibuprofen 600 mg plus acetaminophen 650 mg administered every 6 hours for 24 hours.2 If patients are compliant with these four doses of two different medications, additional analgesics may not be required. These medications can be administered every 6 hours either together or in a staggered fashion based on physician and patient preference. The staggered approach may be desired for patients in whom more frequent medication administration is psychologically beneficial following dental surgery, even though there is no pharmacological benefit in doing so.

It cannot be overstated that the key to success of the 2-4-24 regimen is adherence; patients may need to set alarms in order not to miss any scheduled nighttime doses during the initial 24-hour postoperative period. Some patients may require additional analgesics on an “as needed” basis after the initial 24-hour regimen, with either drug taken alone or in combination. However, if patients still require routine pain medication beyond the initial 48-hour postoperative period despite excellent compliance, re-examination by the dental practitioner is strongly encouraged.

Analgesics can also be given preoperatively to mitigate postoperative pain (preemptive analgesia).16 This strategy could employ acetaminophen, a NSAID, or a glucocorticoid, such as dexamethasone 4 mg orally 30 minutes prior to the procedure.17 Celecoxib 400 mg administered orally 30 minutes prior to the procedure may be the ideal NSAID for preemptive analgesia because it will ameliorate the inflammatory response without delaying wound healing or prolonging bleeding.18 Celecoxib 200 mg given every 12 hours for the initial 24-hour postoperative period could also more safely replace the postoperative ibuprofen 600 mg prescription for patients maintained on anticoagulants such as warfarin, dabigatran, rivaroxaban, or apixaban.


If nociceptive orofacial pain does not resolve spontaneously once the underlying cause is treated, a pharmacologic approach to pain management should be considered. Current research, evidence, and best-practice recommendations support acetaminophen and NSAIDs as the medications of choice to treat nociceptive orofacial pain. Glucocorticoids can also be useful adjuncts. Opioid medications should only be an option after considering acetaminophen, NSAIDs, glucocorticoids, and preemptive analgesia for severe refractory pain.

About The Author

Mark Donaldson, BSP, ACPR, PHARMD
Senior Executive Director, Vizient Pharmacy Advisory Solutions, Irving, Texas; Clinical Professor, School of Pharmacy, University of Montana; Clinical Assistant Professor, School of Dentistry, Oregon Health & Sciences University; Adjunct Professor, Faculty of Dentistry, University of British Columbia; Fellow, American Society of Health-System Pharmacists; Fellow, American College of Healthcare Executives


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