Odontogenic Pain-Clinical Review, Challenges and Evidence for Consideration of Aceclofenac Paracetamol Combination

Odontogenic pain originates from the teeth or their supporting structures, including the mucosa, gingivae, maxilla, mandible, or periodontal membrane. Odontogenic pain entails substantial discomfort and suffering as a subjective and intricate experience, constituting a prevalent symptom of dental and oral ailments. [1] Odontogenic pain can result in social, psychological, and health-economic repercussions for individuals and communities. Untreated odontogenic chronic pain can have far-reaching consequences, potentially exacerbating disability, elevating the risk of tooth falls, triggering feelings of depression, disrupting sleep patterns, deteriorating overall quality of life, and inducing a sense of isolation. [1,2]

Odontogenic Pain: Clinical Review

According to global and regional estimates, the prevalence of odontogenic pain among children and adolescents in India is reportedly about 40%. [3] Odontogenic pain stems from various sources, including dental caries and periodontal infections, inciting inflammation in the oral and dental tissue structures. Dental caries, a primary contributor, introduces bacteria into the pulp via dentinal tubules, triggering inflammation and subsequent pain. Periodontal infections from conditions like gingivitis or periodontitis can also induce discomfort as they impact the tissues surrounding the tooth. Dental procedures such as root canal treatments or extractions can lead to acute postoperative pain due to inflicted trauma. Dental abscesses and impacted teeth can further lead to the development of localized pain and discomfort. [1,4]

In odontogenic pain, inflammation sensitizes nerves, lowering pain thresholds. Dental infections induce immune responses, releasing mediators that amplify tissue inflammation and pain perception. It is important to manage these inflammatory pathways for effective relief and patient comfort.[1,4] Odontogenic pain varies, often with localized discomfort, tenderness, and sensitivity in the affected tooth. Patients report sharp or throbbing pain, worsened by stimuli like heat, cold, and chewing. Swelling, redness, and pain may extend to nearby areas like the jaw or head. Pain intensity varies based on the condition, from mild discomfort to severe agony. [1,4] The approach to evaluation and diagnosis of odontogenic pain is infographically represented here [5]

Figure: Diagnostic chart for abnormal dental pain. Adapted from Ken-ichi Fukuda. Diagnosis and treatment of abnormal dental pain. Journal of Dental Anesthesia and Pain Medicine,2016;16(1):1-8.

Challenges In Addressing Odontogenic Pain Management in India & Current Pain Management Strategies

In India, odontogenic pain poses significant challenges due to limited access to dental care, inadequate oral hygiene practices, and lack of awareness about preventive measures. Cultural beliefs and socioeconomic disparities further contribute to delays in seeking timely treatment. These factors underscore the need for improved oral health education, better access to dental services, and strategies to address barriers to alleviate odontogenic pain and improve oral health outcomes in the Indian population.[6,7] In many parts of the country, patients often resort to self-medication for dental issues, where conventional healthcare intertwines with alternative remedies. In addition, the uninformed use of pharmacological agents can result in inadequate pain relief due to inappropriate selection.[8]

Current pain management strategies for odontogenic pain encompass a multidimensional approach involving pharmacological interventions, local anesthetics, and combination therapies. Various analgesic agents, including paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, novel agents, and combinations of these treatments, are used to manage odontogenic pain. [9,10]

• NSAIDs: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medications known for their potent anti-inflammatory, analgesic, and antipyretic properties. These drugs work by inhibiting the activity of cyclooxygenase enzymes (COX-1 and COX-2), which play a crucial role in producing prostaglandins, which promote inflammation, pain, and fever. NSAIDs effectively alleviate pain and inflammation, making them valuable treatment options for dental pain.[10]
• Paracetamol: Paracetamol medication is recognized for its effective analgesic and antipyretic properties. It acts primarily by inhibiting cyclooxygenase enzymes (COX-1 and COX-2) through their peroxidase functions, reducing the production of prostaglandins responsible for pain and fever. Its ability to alleviate discomfort and fever makes it a valuable option for various dental conditions. Paracetamol also exerts central action by inhibiting prostaglandin synthesis in the brain, contributing to its analgesic and antipyretic effects. [10]
• Opioids: Opioids are a class of potent analgesic medications commonly used for managing moderate to severe pain. They bind to specific brain and spinal cord receptors, modulating pain perception and response.[10]
• Combination of Drugs: Combination therapy involves using multiple pain-relieving agents to enhance their collective effectiveness. This approach leverages the synergistic interactions between medications, such as combining nonsteroidal anti-inflammatory drugs (NSAIDs) with paracetamol.[10]

Aceclofenac Paracetamol Combination Treatment

The concurrent use of a nonsteroidal anti-inflammatory drug (NSAID) and paracetamol leads to a synergistic analgesic effect. These medications operate through distinct mechanisms: the NSAID primarily affects the peripheral region, while paracetamol acts on the central nociceptive pathway. This complementary action coming together may represent a multimodal analgesic approach. It has been shown that the combination of NSAIDs and paracetamol provides superior pain relief compared to paracetamol alone in acute dental pain. [11,12]

Aceclofenac, a highly selective COX-2 inhibitor, demonstrates potent anti-inflammatory effects by reducing the expression of inflammatory mediators like Interleukin (IL-1β), Tumor Necrosis Factor (TNF), and neutrophil adhesion molecules. It selectively inhibits the COX-2 enzyme and hinders the formation of Prostaglandins (PGE2), which contributes to pain. These characteristics make it a preferred choice in treating odontogenic pain. The recommended oral dose of Aceclofenac for odontogenic pain management is 100 mg twice daily.[13]

Paracetamol demonstrates a dual activity by curbing COX-1 and COX-2 through its peroxidase actions, resulting in analgesic and antipyretic effects. Its widely accepted acclaim stems from its adeptness in alleviating pain, reducing fever, and suppressing inflammation.[10]

Aceclofenac and Paracetamol in Odontogenic Pain: Scientific Evidence Review

Aceclofenac Plus Paracetamol Combination Effective for Pain Reduction: Sundaram S et al. conducted a prospective, single-blinded, clinical pilot study among 40 Indian patients in which Aceclofenac 100 mg was combined with paracetamol 325 mg and was administered twice a day to patients post-dental implant placement to assess post-operative pain relief. It was observed that the combination drug administered showed better outcomes in pain perception in 24 hours (p<0.05) and 72 hours (p<0.03). This concludes that the aceclofenac plus paracetamol combination effectively treats postoperative dental pain.[14]

Aceclofenac Effective for Acute Odontogenic Pain: Nagendra SC et al. conducted a randomized open-label comparative study to assess the safety and efficacy of oral analgesics for reducing dental pain. The study included Indian patients (n=50, aged 18-60 years) divided into two groups: one arm receiving aceclofenac 100 mg twice daily, and the other one, diclofenac sodium 50 mg thrice daily. Pain intensity was assessed on a four-point scale (0 = none to 3 = severe) at baseline and specified times (0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 12, 24 h after drug administration). Aceclofenac demonstrated early onset analgesia within 30.6 (±7.34) minutes compared to 72.2 (±21.6) minutes for diclofenac sodium (P < 0.01). With rapid onset and prolonged action, aceclofenac exhibited superior efficacy in managing moderate to severe acute odontogenic pain.[15]

Paracetamol Regimen Effective for Reducing Postoperative Swelling Following Molar Surgery: Bjornsson GA et al. conducted a controlled, randomized, double-blind crossover trial in which patients served as their comparisons in assessing the effectiveness of naproxen 500 mg (twice daily) versus paracetamol 1000 mg (four times daily) over 3 days following third molar surgery. Paracetamol exhibited a significant 22.4% reduction in average swelling on the 3rd day after surgery (p = 0.023) compared to naproxen. The findings suggest that a 3-day paracetamol regimen effectively reduces acute postoperative swelling after third molar surgery.[16]

Advantages of Aceclofenac and Paracetamol Combination Treatment

• Synergistic Effect: The combination of aceclofenac and paracetamol leads to a synergistic effect, enhancing the overall pain-relieving properties.[10]
• Dual Mechanism: Aceclofenac's anti-inflammatory action and paracetamol's analgesic and antipyretic effects may support a comprehensive approach to managing pain and discomfort. [11,12]
• Optimal Pain Relief: The dual action addresses multimodal analgesia, providing more effective pain relief than using each drug alone. [10,11,12,13]
• Enhanced Patient Comfort: The combination improves patient comfort by tackling pain and inflammation, allowing for a prompt recovery process. [10,11,12,13,14,15,16]
• The recommended dosage for the use of combination therapy is Aceclofenac (100 mg) plus Paracetamol (325 mg) twice a day. [10,13,16]

Clinical Care Pointers

• Odontogenic pain stems from dental structures like teeth, mucosa, gingivae, maxilla, mandible, and periodontal membrane, leading to significant discomfort and suffering in dental and oral conditions.
• Multidimensional treatment approaches involving pharmacological interventions, local anesthetics, and combination therapies are employed. Analgesic agents like NSAIDs, paracetamol, opioids, and combination treatment could be utilized.
• Combining NSAID and paracetamol allows a synergistic analgesic effect targeting peripheral and central pathways. This multimodal approach offers superior pain relief compared to paracetamol alone.
• Clinical trials support the efficacy of the aceclofenac-paracetamol combination in managing acute odontogenic pain. Early onset analgesia, pain relief, and better postoperative outcomes have been observed.

The synergistic combination of Aceclofenac and Paracetamol could be considered a comprehensive approach to managing odontogenic pain effectively. This combination therapy supports pain relief and improves patient comfort, addressing the complex pain intricately originating from dental structures and their supporting tissues. [10,11,12,13,14,15,16]

References:

1. Renton, T. Dental (odontogenic) pain. Reviews in Pain,2011;5(1), 2–7. https://doi.org/10.1177/204946371100500102

2. Oberoi, S. S., Hiremath, S. S., Yashoda, R., Marya, C., & Rekhi, A. Prevalence of various orofacial pain symptoms and their overall impact on quality of life in a tertiary care hospital in India. Journal of Maxillofacial and Oral Surgery,2014;13(4):533–538. https://doi.org/10.1007/s12663-013-0576-6

3. Pentapati, K. C., Yeturu, S. K., & Siddiq, H. Global and regional estimates of dental pain among children and adolescents—systematic review and meta-analysis. European Archives of Paediatric Dentistry: Official Journal of the European Academy of Paediatric Dentistry, 2021;22(1):1–12. https://doi.org/10.1007/s40368-020-00545-7

4. J. R. Allison, S. J. Stone & M. Pigg. The painful tooth: mechanisms, presentation and differential diagnosis of odontogenic pain.Oral Surgery,2020; 13(4):309–320. https://doi.org/10.1111/ors.12481

5. Ken-ichi Fukuda. Diagnosis and treatment of abnormal dental pain. Journal of Dental Anesthesia and Pain Medicine,2016;16(1):1-8 DOI:10.17245/jdapm.2016.16.1.1

6. Pritma Singh, Afshan Bey, N. D. Gupta. Dental health attitude in Indian society. Journal of International Society of Preventive & Community Dentistry,2013;3(2):81. https://doi.org/10.4103/2231-0762.122444

7. Sanjay Miglani. Burden of Dental Caries in India: Current Scenario and Future Strategies. International Journal of Clinical Pediatric Dentistry,2020;13(2):155–159. https://doi.org/10.5005/jp-journals-10005-1733

8. Arun K Simon, Ashwini Rao, Gururaghavendran Rajesh, Ramya Shenoy, Mithun B. H Pai. Trends in self-medication for dental conditions among patients attending oral health outreach programs in coastal Karnataka, India. Indian Journal Of Pharmacology,2015;47(5):524-529 https://doi.org/10.4103/0253-7613.165195

9. Sung-Jin Kim, Jeong Taeg Seo. Selection of analgesics for the management of acute and postoperative dental pain: a mini-review. J Periodontal Implant Sci. 2020 Apr;50(2):68-73 https://doi.org/10.5051/jpis.2020.50.2.68

10. Joseph V. Pergolizzi, Peter Magnusson, Jo Ann LeQuang, Christopher Gharibo & Giustino Varrassi. The pharmacological management of dental pain. Expert Opinion on Pharmacotherapy,2020;21(9):1-11 https://www.researchgate.net/publication/339087047_The_pharmacological_management_of_dental_pain

11. Graham, Garry & Davies, Michael & Day, Richard & Mohamudally, Anthoulla &Scott, Kieran. The modern pharmacology of paracetamol: Therapeutic actions, mechanism of action, metabolism, toxicity, and recent pharmacological findings. Inflammopharmacology,2013;21. https://doi.org/10.1007/s10787-013-0172-x

12. Mohamed Amine Msolli, MD, Adel Sekma, MD, Marwa Toumia, MD, Khaoula Bel Haj Ali, MD, Mohamed Hassen Khalil, MD,Mohamed Habib Grissa, MD, Wahid Bouida, MD, Kaouthar Beltaief, MD,Asma Zorgati, MD, Mehdi Methamem, MD, Asma Belguith, MD,Riadh Boukef, MD, Hamdi Boubaker, MD and Semir Nouira, MD. Acetaminophen, Nonsteroidal Anti-inflammatory Drugs, or Combination of Both Analgesics in Acute Posttrauma Pain: A Randomized Controlled Trial. Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine, 2021;28(2), 155–163. https://doi.org/10.1111/acem.14169

13. Karthik R Mohan, Mohan Narayanan, Pethagounder Thangavel Ravikumar, Saramma M Fenn, Sabitha Gokulraj, Amirthaleka. Evaluation of NSAIDs in Acute Odontogenic Pain: A Quadriblind Study. World Journal of Dentistry 2019;10(5):384–389. https://doi.org/10.5005/jp-journals-10015-1649

14. Sundaram Surendran, Sahana Selvaganesh, Thiyaneswaran Nesappan, Vishnu Priya Veeraraghavan & Rajalakshmanan Eswaramoorthy. Post-operative pain management using two drugs following dental implant surgery among Indians. Bioinformation,2023;19(4):476-478 https://doi.org/10.6026/97320630019476

15. Nagendra S. Chunduri, Tanveer Kollu, Venkateswarulu R. Goteki, Kiran K. Mallela, Krishnaveni Madasu. Efficacy of aceclofenac and diclofenac sodium for relief of postoperative pain after third molar surgery: A randomized open-label comparative study. Journal of Pharmacology & Pharmacotherapeutics,2013;4(2):144–145. https://doi.org/10.4103/0976-500x.110910

16. Bjørnsson, G. A., Haanaes, H. R., & Skoglund, L. A. Naproxen 500 mg bid versus Acetaminophen 1000 mg qid: Effect on Swelling and Other Acute Postoperative Events after Bilateral Third Molar Surgery. Journal of Clinical Pharmacology,2003;43(8):849–858. https://doi.org/10.1177/0091270003255361