Effect of Diphenhydramine Mouthwash on Pain During Inferior Alveolar Nerve Block Injection
Abstract
Introduction: Pain management in dental procedures is a central concern, as discomfort during local anesthesia injections often reduces patient compliance and increases procedural anxiety. The inferior alveolar nerve block (IANB) is a commonly employed technique for mandibular anesthesia but is frequently associated with injection pain. Diphenhydramine, an antihistamine with local anesthetic properties, has recently gained attention as a topical analgesic agent. However, evidence on its clinical efficacy in reducing injection pain during IANB is limited. This study aimed to evaluate the effect of diphenhydramine mouthwash on pain perception during inferior alveolar nerve block injection in patients undergoing oral surgical procedures. Materials and Methods: In this randomized clinical trial, 39 patients requiring bilateral IANB at the Faculty of Dentistry, Alborz University of Medical Sciences (2024), were enrolled. Using a split-mouth design, one side of the mandible was randomly assigned to rinsing with 15 mL diphenhydramine mouthwash for 30 seconds, while the contralateral side was rinsed with normal saline. Pain intensity during injection was assessed 5 minutes after rinsing using a 10-point Visual Analogue Scale (VAS). Statistical analysis was performed using paired t-tests, with significance set at p < 0.05. Results: The mean VAS pain score was significantly lower in the diphenhydramine group (3.31±0.86) compared to the control group (4.92±0.84) (p < 0.001). The analgesic effect was consistent across age groups (19–79 years), genders, and different types of surgical procedures (tooth extraction, implant placement). Conclusion: Diphenhydramine mouthwash effectively reduced pain during IANB injection and may serve as a simple, low-cost adjunct to improve patient comfort in oral surgery. Future studies should focus on optimizing dosing protocols and confirming long-term clinical benefits. Keywords: Diphenhydramine mouthwash; Inferior alveolar nerve block; Local anesthesia; Pain management; Clinical trial.
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16. de Souza Melo MR, Sabey MJS, Lima CJ, de Almeida Souza LM, Groppo FC. The effect of two injection speeds on local anesthetic discomfort during inferior alveolar nerve blocks. Anesthesia Progress. 2015;62(3):106.
17. Tavakoli A, Khoramiyan S. The effect of chlorhexidine and benzydamine on gingivitis. Iranian Journal of Pediatric Dentistry. 2015;11(1):65–72.
18. Bendgude V, Walimbe H, Bijle MNA, Muchandi S, Deshpande R, Dolas A, et al. Comparative evaluation of the efficacy of topical anesthetics in reducing pain during administration of injectable local anesthesia in children. World Journal of Dentistry. 2016;5(2):129–33.
19. Khoshkhoonejad A, Khorsand A, Rastgar F. A comparative study on Benzydamine HCL 0.5% and Acetaminophen Codeine in pain reduction following periodontal surgery. Journal of Dental Medicine. 2004;17(2):39–44.
20. Sio TT, Le-Rademacher JG, Leenstra JL, Loprinzi CL, Rine G, Curtis A, et al. Effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo on radiotherapy-related oral mucositis pain: The Alliance A221304 randomized clinical trial. JAMA. 2019;321(15):1481–90.
21. Armfield JM, Milgrom P, Armfield J. A clinician guide to patients afraid of dental injections and numbness. SAAD Dig. 2011;27(7):33–9.
22. Lim HW, Mahmod NI, Zaki FHA, Tan FY, Balasundram S, Adnan TH. Wisdom tooth surgery complications—Local anaesthesia versus general anaesthesia. Open Journal of Stomatology. 2019;9(03):51.
23. Ahmadi A, Khalili M, Hajikhani R, Safari N, Nahri-Niknafs B. Anti-inflammatory effects of two new methyl and morpholine derivatives of diphenhydramine on rats. Medicinal Chemistry Research. 2012;21:3532–40.
2. Irby WB, Baldwin KH. Emergencies and urgent complications in dentistry. 1965.
3. Kazari R, Razavi BM, Amiri Tehranizadeh Z, Bazzaz F, Sedigheh B. Another look at local anesthetics: An overview of antimicrobial properties. Medical Journal of Mashhad University of Medical Sciences. 2022;65(2):468–92.
4. Scully C. Handbook of Oral Disease: Diagnosis and Management. Martin Dunitz; 2001.
5. Glick M, Greenberg MS. Burket’s Oral Medicine: Diagnosis and Treatment. 2003.
6. Little JW, Miller C, Rhodus NL. Dental Management of the Medically Compromised Patient. Elsevier Health Sciences; 2017.
7. Donaldson D, Meechan JG. A comparison of the effects of EMLA cream and topical 5% lidocaine on discomfort during gingival probing. Anesthesia Progress. 1995;42(1):7.
8. Franz-Montan M, De Paula E, Groppo F, Silva A, Ranali J, Volpato M. Liposomal delivery system for topical anaesthesia of the palatal mucosa. Br J Oral Maxillofac Surg. 2012;50(1):60–4.
9. Goldberg S, Reader A, Drum M, Nusstein J, Beck M. Comparison of the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques. J Endod. 2008;34(11):1306–11.
10. Kosaraju A, Vandewalle KS. A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: a clinical evaluation. J Am Dent Assoc. 2009;140(1):68–72.
11. MG JM, San Hipólito Marín L. A comparative study of direct mandibular nerve block and the Akinosi technique. Medicina Oral. 2003;8(2):143–9.
12. Moghaddam N, Pirzadeh Ashraf A, Bakhtiari F, Mirzaali F, Pournasrollah A. The effect of oral analgesic premedication on the success rate of inferior alveolar nerve block for teeth with irreversible pulpitis: A randomized clinical trial. Journal of Dental Materials and Techniques. 2024;13(1):14–8.
13. Ghafoor H, Haroon S, Atique S, Huda AU, Ahmed O, Khair AOMB, et al. Neurological complications of local anesthesia in dentistry: a review. Cureus. 2023;15(12).
14. Ulu M, Etöz OA, Demirbaş AE, Çanakçı FGY, Akçay H. Effect of warming of local anesthesia on pain and anesthesia duration before wisdom tooth extraction. Cukurova Medical Journal. 2019;44(3):845–9.
15. St George G, Morgan A, Meechan J, Moles DR, Needleman I, Ng YL, et al. Injectable local anaesthetic agents for dental anaesthesia. Cochrane Database of Systematic Reviews. 2018;(7).
16. de Souza Melo MR, Sabey MJS, Lima CJ, de Almeida Souza LM, Groppo FC. The effect of two injection speeds on local anesthetic discomfort during inferior alveolar nerve blocks. Anesthesia Progress. 2015;62(3):106.
17. Tavakoli A, Khoramiyan S. The effect of chlorhexidine and benzydamine on gingivitis. Iranian Journal of Pediatric Dentistry. 2015;11(1):65–72.
18. Bendgude V, Walimbe H, Bijle MNA, Muchandi S, Deshpande R, Dolas A, et al. Comparative evaluation of the efficacy of topical anesthetics in reducing pain during administration of injectable local anesthesia in children. World Journal of Dentistry. 2016;5(2):129–33.
19. Khoshkhoonejad A, Khorsand A, Rastgar F. A comparative study on Benzydamine HCL 0.5% and Acetaminophen Codeine in pain reduction following periodontal surgery. Journal of Dental Medicine. 2004;17(2):39–44.
20. Sio TT, Le-Rademacher JG, Leenstra JL, Loprinzi CL, Rine G, Curtis A, et al. Effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo on radiotherapy-related oral mucositis pain: The Alliance A221304 randomized clinical trial. JAMA. 2019;321(15):1481–90.
21. Armfield JM, Milgrom P, Armfield J. A clinician guide to patients afraid of dental injections and numbness. SAAD Dig. 2011;27(7):33–9.
22. Lim HW, Mahmod NI, Zaki FHA, Tan FY, Balasundram S, Adnan TH. Wisdom tooth surgery complications—Local anaesthesia versus general anaesthesia. Open Journal of Stomatology. 2019;9(03):51.
23. Ahmadi A, Khalili M, Hajikhani R, Safari N, Nahri-Niknafs B. Anti-inflammatory effects of two new methyl and morpholine derivatives of diphenhydramine on rats. Medicinal Chemistry Research. 2012;21:3532–40.
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| Issue | Vol 12, No 3 (Summer 2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Diphenhydramine mouthwash; Inferior alveolar nerve block; Local anesthesia; Pain management; Clinical trial. | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Arabi Darehdor A, Salmani Z, Gharehsheikhloo M. Effect of Diphenhydramine Mouthwash on Pain During Inferior Alveolar Nerve Block Injection. J Craniomaxillofac Res. 2025;12(3):156-167.


