223: Effect of Ozone Infiltration in Temporomandibular Joint Arthralgia: Randomized Clinical Trial

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic secondary musculoskeletal pain, Assessment and Measurement of Pain/Nociception, Quantitative Sensory testing (static and dynamic, e.g., HPT, PPT, CPM, TSP, offset analgesia), Treatment/management

Background and Aims: Temporomandibular disorders (TMD) affect the temporomandibular joint (TMJ), masticatory muscles, and related structures. TMJ arthralgia has a prevalence of about 7% and is often treated with medication, which may be limited by adverse effects in refractory cases. Minimally invasive approaches such as ozone therapy have been proposed but remain underresearched. This double-blind randomized clinical trial aimed to compare intra-articular ozone gas infiltration versus saline solution in adults with bilateral TMJ arthralgia diagnosed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD).

Methods: Participants ≥18 years with bilateral TMJ arthralgia for >3 months, diagnosed using DC/TMD, were included. In a split-mouth design, each participant was randomly assigned to receive 1 mL ozone gas (10 μg) in one TMJ and 1 mL saline solution in the other TMJ. Four applications were performed at 7-day intervals, with follow-up at 1 and 4 months. Joint pain was assessed using the Numeric Visual Scale (NVS) and Patient Global Impression of Change (PGIC). Somatosensory testing included WUR, PPT, and CPM in the TMJ region and thenar muscle. Psychosocial measures included DASS-21, PCS, and GCPS. Analyses used SPSS.

Results: Of 447 assessed participants, 21 were included (42 TMJs; 17 women; mean age 32.1 years). Pain scores decreased from baseline to follow-up in both ozone and saline, with no between-intervention differences at any time point. PGIC indicated improvement at 1 and 4 months, predominantly “better” and “moderately better,” respectively. Somatosensory outcomes (WUR, PPT, CPM) in the TMJ region and thenar muscle showed no significant differences. DASS-21 showed no significant change; PCS and GCPS decreased from baseline to 4 months, indicating reduced catastrophizing, pain intensity, and disability.

Conclusions: In adults with TMJ arthralgia, intra-articular ozone and saline reduced pain (NVS) over follow-up, with no between-intervention differences, suggesting similar effects.

References: 1. De Leeuw R, Klasser GD. Orofacial pain: Guidelines for assessment, diagnosis, and management. 6th ed. Quintessence Publishing; 2018.
2. Valesan LF, Da-Cas CD, Réus JC, Denardin ACS, Garanhani RR, Bonotto D, et al. Prevalence of temporomandibular joint disorders: A systematic review and meta-analysis. Clin Oral Investig. 2021;25:441-453. doi:10.1007/s00784-020-03710-w.
3. Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, et al. Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications. J Oral Facial Pain Headache. 2014;28:6-27. doi:10.11607/jop.1151.
4. Okeson JP. Management of temporomandibular disorders and occlusion. 8th ed. Mosby; 2019.
5. Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. 2020;180:114147. doi:10.1016/j.bcp.2020.114147.
6. Daif ET. Role of intra-articular ozone gas injection in the management of internal derangement of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:e10-e14. doi:10.1016/j.tripleo.2011.08.006.
7. Dogan M, Dogan DO, Duger C, et al. Effects of high-frequency bio-oxidative ozone therapy in temporomandibular disorder-related pain. Med Princ Pract. 2014;23:507-510. doi:10.1159/000365355.
8. Sagai M, Bocci V. Mechanisms of action involved in ozone therapy: Is healing induced via a mild oxidative stress? Med Gas Res. 2011;1:29. doi:10.1186/2045-9912-1-29.
9. Celakil T, Muric A, Roehlig BG, Evlioglu G, Keskin H. Effect of high-frequency bio-oxidative ozone therapy for masticatory muscle pain: A double-blind randomized clinical trial. J Oral Rehabil. 2017;44:442-451. doi:10.1111/joor.12509.
10. Manoto SL, Maepa MJ, Motaung SK. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis. Saudi J Biol Sci. 2018;25:672-679. doi:10.1016/j.sjbs.2017.03.005.
11. Rodríguez-Merchán EC, De la Corte-Rodríguez H, Román-Belmonte JM. Intraarticular injections of ozone gas in knee osteoarthritis. In: Rodríguez-Merchán EC, Gómez-Cardero P, editors. Comprehensive treatment of knee osteoarthritis. Springer; 2020. doi:10.1007/978-3-030-42091-7_10.
12. Chirumbolo S, Valdenassi L, Tirelli U, Ricevuti G, Pandolfi S, Vaiano F, et al. The oxygen-ozone adjunct medical treatment according to the protocols from the Italian Scientific Society of Oxygen-Ozone Therapy: How ozone applications in the blood can influence clinical therapy success via the modulation of cell biology and immunity. Biology (Basel). 2023;12(12):1512. doi:10.3390/biology12121512.
13. Jeyaraman M, Jeyaraman N, Ramasubramanian S, et al. Ozone therapy in musculoskeletal medicine: A comprehensive review. Eur J Med Res. 2024;29:398. doi:10.1186/s40001-024-01371-9.
14. Yamaner FE, Celakil T, Gökcen Roehlig B. Comparison of the efficiency of two alternative therapies for the management of temporomandibular disorders. Cranio. 2022;40(3):189-194. doi:10.1080/08869634.2019.1696502.
15. Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: Updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c869. doi:10.1136/bmj.c869.
16. Laskin DM. Needle placement for arthrocentesis. J Oral Maxillofac Surg. 1998;56:907. doi:10.1016/S0278-2391(98)90728-0.
17. Durham J, Al-Baghdadi M, Baad-Hansen L, et al. Self-management programmes in temporomandibular disorders: Results from an international Delphi process. J Oral Rehabil. 2016;43(12):929-936. doi:10.1111/joor.12447.
18. Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, et al. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain. 2003;106(3):337-345. doi:10.1016/j.pain.2003.08.001.
19. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19. doi:10.1016/j.pain.2004.09.012.
20. Edwards RR, Dworkin RH, Turk DC, et al. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. Pain. 2016;157(9):1851-1871. doi:10.1097/j.pain.0000000000000575.
21. Ferreira-Valente MA, Pais-Ribeiro JL, Jensen MP. Validity of four pain intensity rating scales. Pain. 2011;152(10):2399-2404. doi:10.1016/j.pain.2011.07.005.
22. Domingues L, Cruz EB. Adaptação cultural e contributo para a validação da escala Patient Global Impression of Change. Ifisionline. 2011;2(4):31-37.
23. Rolke R, Baron R, Maier C, Tölle TR, Treede DR, Beyer A, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain. 2006;123(3):231-243. doi:10.1016/j.pain.2006.01.041.
24. Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, et al. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015;19(6):805-806. doi:10.1002/ejp.605.
25. Gehling J, Mainka T, Vollert J, Pogatzki-Zahn EM, Maier C, Enax-Krumova EK. Short-term test–retest reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing. BMC Neurol. 2016;16:125. doi:10.1186/s12883-016-0641-1.
26. Santos-Silva RS, Conti PC, Lauris JR, Da Silva RO, Pegoraro LF. Pressure pain threshold in the detection of masticatory myofascial pain: An algometer-based study. J Orofac Pain. 2005;19(4):318-324.
27. Antony MM, Bieling PJ, Cox BJ, Enns MW, Swinson RP. Psychometric properties of the 42-item and 21-item versions of the Depression Anxiety Stress Scales in clinical groups and a community sample. Psychol Assess. 1998;10(2):176-181. doi:10.1037/1040-3590.10.2.176.
28. Vignola RCB, Tucci AM. Adaptation and validation of the Depression, Anxiety, and Stress Scale (DASS) to Brazilian Portuguese. J Affect Disord. 2014;155:104-109. doi:10.1016/j.jad.2013.10.031.
29. Sullivan MJL, Stanish W, Waite H, Sullivan M, Tripp DA. Catastrophizing, pain, and disability in patients with soft-tissue injuries. Pain. 1998;77(3):253-260. doi:10.1016/S0304-3959(98)00017-2.
30. Von Korff M, Ormel J, Keefe FJ, Dworkin SF. Grading the severity of chronic pain. Pain. 1992;50(2):133-149. doi:10.1016/0304-3959(92)90154-4.
31. International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia. 2020;40(2):129-221. doi:10.1177/0333102419893823.
32. Rossi SS, Greenberg MS, Liu F, Steinkeler A. Temporomandibular disorders. Med Clin North Am. 2014;98(6):1353-1384. doi:10.1016/j.mcna.2014.08.006.
33. Dworkin RH, Turk DC, Farrar JT, et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113(1-2):9-19. doi:10.1016/j.pain.2004.09.012.
34. Reyes JMV, Castillo MG. Ozonetherapy as an alternative to pain treatment in temporomandibular disorders. Acta Sci Neurol. 2021;4(3):46-52. doi:10.4172/2167-0846.C1.012.
35. Cömert Kiliç S, Gürsac Çeli KM. Does intra-articular medical ozone therapy applied at different concentrates improve outcomes of temporomandibular joint osteoarthritis? A randomized clinical trial. J Craniomaxillofac Surg. 2025;Advance online publication. doi:10.1016/j.jcms.2025.02.016.
36. Chen H, Nackley A, Miller V, Diatchenko L, Maixner W. Multisystem dysregulation in painful temporomandibular disorders. J Pain. 2013;14(9):983-996. doi:10.1016/j.jpain.2013.03.010.
37. Lopes de Jesus CC, Dos Santos FC, De Jesus LMO B, Monteiro I, Sant'Ana MSSC, Trevisani VFM. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. PLoS One. 2017;12(7):e0179185. doi:10.1371/journal.pone.0179185.

Presenting Author: Adriana Battisti Archer
Submitting Author: Adriana Archer

Senior Author: Beatriz Dulcineia Mendes de Souza

IASP 2026 Global Year theme of Neuropathic Pain: No

• Adriana Battisti Archer: DDS, MSc - Federal University of Santa Catarina
• Lígia Figueiredo Valesan: DDS, MSc, PhD - Federal University of Santa Catarina
• Ana Paula Braghini: DDS, MSc - Federal University of Santa Catarina
• Gilberto Melo: DDS, MSc, PhD - Federal University of Santa Catarina
• Giancarlo De La Torre Canales: DDS, MSc, PhD - Karolinska Institutet
• Beatriz Dulcineia Mendes de Souza: DDS, MSc, PhD - Federal University of Santa Catarina