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Novel Approaches to Pain Management

While ibuprofen and acetaminophen are often the first choice in post-procedure analgesics, other options may be helpful in pain management.

This course was published in the July/August 2023 issue and expires August 2026. The authors have no commercial conflicts of interest to disclose. This 2 credit hour self-study activity is electronically mediated.

AGD Subject Code: 340

Educational ­Objectives

After reading this course, the participant should be able to:

1. Identify the rate of opioid prescribing in the dental setting.
2. Note the populations at risk for opioid misuse.
3. Discuss the role of nonsteroidal anti-inflammatory drugs in post-procedure pain management.
4. Explain the possible use of novel approaches in post-surgical pain management.

Opioid alternatives for post-operative pain control have received significant attention in recent years due to an increase in opioid addiction and overdose.1 Although the number of opioid prescriptions written by dentists has decreased in the last decade or so, oral health professionals are still one of the top prescribers of these medications. Oral health professionals wrote 12.2% of all immediate-release opioid prescriptions in 2007, with that rate dropping to 8.6% in 2017.1,2 What was once a routine analgesic for common dental procedures became part of America’s opioid crisis.

Vulnerable Populations

Teenagers and young adults are especially vulnerable to opioid abuse. Many of these patients are first exposed to opioids following third molar extractions. Sixty percent to 70% of opioid prescriptions written by oral health professionals were dispensed by oral and maxillofacial surgeons to ensure a comfortable recovery,3 and it is estimated that 15% of opioid prescriptions end up being used recreationally.2

While not an exhaustive literature review, this article aims to provide a clinically useful overview of evidence-based best practices in analgesia prescribing while highlighting two novel drugs with clinical applications that may benefit dental patients.

Nonsteroidal Anti-Inflammatory Drugs

The evidence suggests nonsteroidal anti-inflammatory drugs (NSAIDs) on their own, or in combination with acetaminophen, should be the first-line treatment for post-procedure pain.1,4 Several randomized controlled trials found that combining NSAIDs and acetaminophen may provide better analgesia than ibuprofen or acetaminophen alone.1,4 More important, research also suggests the combination of NSAIDs and acetaminophen may provide more effective analgesia than opioids alone, and with fewer side effects.4

While opioids act on the mu opioid receptor, NSAIDs and acetaminophen have different mechanisms of action. Specifically, NSAIDs are competitive cyclooxygenase (COX) inhibitors that decrease production of inflammatory mediators.4 Acetaminophen acts centrally to control pain through several proposed mechanisms and is also a weak COX inhibitor.1

Patient and Procedure Specific

Prescribing an appropriate pain management regimen is patient and procedure specific. It begins with a thorough patient assessment; in addition, case management should include patient education regarding post-procedure expectations. By better understanding a patient’s expectations and history with pain management, the clinician can better formulate an appropriate pain procedure plan.

Pain management strategies should use multimodal therapy and be stratified based on the expected level of discomfort.1

Mild post-procedure pain can be expected from many general dental procedures. Examples include simple root canals, restorations, crown preparations, simple extractions, and single implant placement. For this type of pain, 400 to 600 mg ibuprofen taken every 4 to 6 hours as needed for pain typically provides sufficient analgesia.

For more complex procedures — such as complex root canals and retreatments, apicoectomies, simple tissue grafts, surgical extractions, and multiple implant placements with grafting — moderate pain can be expected. Studies support 400 to 600 mg ibuprofen in combination with 325 to 500 mg acetaminophen every 4 to 6 hours to manage moderate pain for the first 24 hours, followed by the combination every 4 to 6 hours as needed.1,4

While not common in general dental procedures, severe pain can be expected following complex oral and maxillofacial surgery, as well as extensive tissue grafts. In these cases, 400 to 600 mg ibuprofen and 325 to 500 mg acetaminophen every 4 to 6 hours for the first 24 hours can be supplemented with 5 mg of hydrocodone or oxycodone every 4 to 6 hours as needed for breakthrough pain.1,4 Following 24 to 48 hours, the opioid may be eliminated.4

For patients without contraindications to these medications, the maximum daily dose for ibuprofen is 3,200 mg, while the maximum daily dose of acetaminophen is 3,000 mg (Table 1).1,4 The United States Food and Drug Administration maximum total daily dose of acetaminophen increases to 4,000 mg with the direction of a healthcare professional.5

The combination of ibuprofen and acetaminophen became commercially available in 2020 in a pill that contains 125 mg ibuprofen and 250 mg acetaminophen per tablet. The combination is innovative and may be beneficial, as it has the potential to simplify instructions for patients by having them take a combination pill instead of two separate medications.

However, the commercially available dose may present a challenge for post-procedure pain management in dentistry. In the case of moderate pain, for example, where the suggestion is 400 to 600 mg of ibuprofen, a patient would require four tablets. These same four tablets would also include 1,000 mg of acetaminophen, which may exceed the maximum daily dose if taken every 4 to 6 hours as recommended.

For some patients, this method of pain relief may not be possible, as NSAIDs should be avoided in those who have an NSAID allergy or risk for gastric ulcers and renal issues, or a history of cardiovascular conditions, such as a coronary artery bypass graft, myocardial infarction or atrial fibrillation.6 Additionally, NSAIDs should be avoided in the third trimester of pregnancy.6

Acetaminophen should not be used by patients with liver issues. For these individuals, novel approaches to post-procedural pain management are especially promising.

Liposomal Bupivacaine

Whether used alone or in combination with acetaminophen, NSAIDs may offer significant analgesia for patients following dental procedures. However, novel long-acting anesthetics and sublingual opioids pose an alternative that warrants exploration.

Liposomal bupivacaine is an innovative injectable local anesthetic intended for single-dose infiltration in patients ages 6 and older. Oral health professionals are certainly comfortable using local anesthesia for intraoperative analgesia. The use of bupivacaine in the dental setting, especially during the removal of third molars, can provide pain control for several hours following the procedure (Figure 1).7

Like traditional injectable bupivacaine, which has high protein binding and is highly lipid soluble, liposomal bupivacaine blocks voltage-gated sodium channels to prevent membrane depolarization and the conduction of pain signals. While traditional bupivacaine can last for several hours, the time-released nature of the liposomal granules allows for a 3- to 4-day duration of action.7

Liposomal bupivacaine is injected via infiltration bucally along each surgical site upon completion of surgery. The liposomal structure degrades slowly over time, releasing the bupivacaine contained within. This slow degradation and drug release accounts for its prolonged pain-relieving action.

Multimodal approaches to post-surgical pain management — including the use of liposomal bupivacaine — result in high levels of patient satisfaction according to a systematic review of 405 patients undergoing plastic surgery procedures.8 Additionally, patients who were treated with liposomal bupivacaine were less likely to need supplemental analgesics, such as opioids.8

The utility of liposomal bupivacaine has been studied for post-surgical pain relief following third molar surgery. Lieblich and Danesi9 demonstrated that liposomal bupivacaine was significantly more effective than a placebo in these cases. They also found that mean pain scores were significantly lower in the liposomal bupivacaine group, a finding of great clinical relevance.9

While the use of an extended release, long-acting local anesthetic intraorally might pose functional challenges for patients, the analgesic benefits may outweigh these concerns. The use of time-released bupivacaine has not been approved for use in pediatric patients younger than 6 and may not be appropriate for patients with special needs due to the risk of prolonged numbness and self-injury. However, liposomal bupivacaine offers promising potential for post-treatment pain control

FIGURE 1. Model of a bupivacaine molecule. An injectable local anesthetic, liposomal bupivacaine holds promise as a novel alternative for long-lasting post-operative pain management.

Sublingual Sufentanil Tablets

Sublingual sufentanil tablets offer another novel approach to pain management with possible applications in dental surgery. Sufentanil is a synthetic opioid that acts on the mu opioid receptors, resulting in potent analgesia. Compared to other opioids, such as morphine or hydromorphone, sufentanil has no clinically relevant metabolites and its dosage does not need to be adjusted for age.

While sublingual sufentanil is still an opioid and carries abuse potential, it is not indicated for self-administration. Rather, it is administered in-office by a clinician using a single-dose applicator, thus removing the potential for patient self-dosing outside of healthcare settings.10

Clinical studies demonstrate high efficacy following abdominal and orthopedic surgeries, including patients with complex medical histories. Sublingual sufentanil was found to have an onset of 15 minutes and a duration of up to 12 hours, with only 3% of patients reporting ineffective analgesia.10

Another study found similar results up to 12 hours, with only 3.7% of patients taking sublingual sufentanil requiring rescue analgesia, compared to 18.5% of patients on a placebo.11 No clinically relevant adverse outcomes were reported.11

While the existing studies demonstrate the promising application in general surgery, there have yet to be studies evaluating the efficacy of sublingual sufentanil on post-operative dental pain. However, sublingual sufentanil tablets have good potential for clinical use following significant oral and maxillofacial surgeries — although further research is needed to justify its introduction into dental practice.


The evidence is clear that opioids are not indicated as first-line analgesics for mild to moderate pain following routine dental procedures. Opioid-sparing strategies are highly effective when using alternatives such as NSAIDs alone or in combination with acetaminophen.

Opioid analgesia is effective in controlling postoperative pain, but poses risks for dependence and side effects, such as nausea, constipation, and drowsiness. Therefore, opioids should be reserved for complex dental surgery as needed for breakthrough pain. Clinicians may also consider a multimodal approach with use of long-acting local anesthetics to delay the onset of postprocedural pain.

Alternatives, such as liposomal bupivacaine and sublingual sufentanil, have great potential in controlling post-operative discomfort. Liposomal bupivacaine is a time-released local anesthetic that, when infiltrated into the surgical site, can produce several days of pain relief. In addition, sublingual sufentanil tablets may be a future option for dentists to provide patients with the powerful analgesia of an opioid — but with few of the side effects.

Sublingual sufentanil tablets have the benefit of being delivered postsurgically by a healthcare professional, avoiding the possibility of self-dosing outside of the dental office. With more dental-specific studies, new management strategies may soon be available for oral health professionals to consider.


  1. Wehler CJ, Panchal NH, Cotchery DL III, et al. Alternatives to opioids for acute pain management after dental procedures. J Am Dent Assoc. 2021;152:641–652.
  2. Moore PA. Pain Management in Dentistry: A Changing and Challenging Landscape Webinar. Sept. 2, 2016. Chicago. American Dental Association.
  3. Hersh EV, Moore PA, Grosser T, et al. Nonsteroidal anti-inflammatory drugs and opioids in postsurgical dental pain. J Dent Res. 2020;99:777–786.
  4. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions. J Am Dent Assoc. 2013;144:898–908.
  5. Acetaminophen safety: Be cautious but not afraid. Available at: http/​:/​/​​pain/​acetaminophen-safety-be-cautious-but-not-afraid. Accessed October 10, 2022.
  6. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Available at: https:/​/​​books/​NBK547742/​. Accessed October 10, 2022.
  7. Kaye AD, Novitch MB, Carlson SF, et al. The role of Exparel plus Meloxicam for postoperative pain management. Curr Pain Headache Rep. 2020;24:6.
  8. Vyas KS, Rajendran S, Morrison SD, et al. Systematic review of liposomal bupivacaine (Exparel) for postoperative analgesia. Plast Reconstr Surg. 2016;138:748e–756e.
  9. Lieblich SE, Danesi H. Liposomal bupivacaine use in third molar impaction surgery: INNOVATE Study. Anesth Prog. 2017;64:127–135.
  10. Hutchins JL, Leiman D, Minkowitz HS, Jove M, DiDonato KP, Palmer PP. An open-label study of sufentanil sublingual tablet 30 mcg in patients with postoperative pain. Pain Med. 2018;19:2058–2068.
  11. Minkowitz HS, Leiman D, Melson T, Singla N, DiDonato KP, Palmer PP. Sufentanil sublingual tablet 30 mcg for the management of pain following abdominal surgery: A randomized, placebo-controlled, phase 3 study. Pain Practice. 2017;17:848–858.

From Dimensions of Dental Hygiene. July/August 2023; 21(7):36, 42-45.

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