Botulinum Toxin for Treating Temporomandibular Disorders: What is the Evidence?

Aims: To systematically review the scientific literature for evidence concerning the clinical use of botulinum toxin (BTX) for the management of various temporomandibular disorders (TMDs). Methods: A comprehensive literature search was conducted in the Medline, Web of Science, and Cochrane Library databases to find randomized clinical trials (RCT) published between 2000 and the end of April 2021 investigating the use of BTX to treat TMDs. The selected articles were reviewed and tabulated according to the PICO (patients/problem/population, intervention, comparison, outcome) format. Results: A total of 24 RCTs were selected. Nine articles used BTX injections to treat myofascial pain, 4 to treat temporomandibular joint (TMJ) articular TMDs, 8 for the management of bruxism, and 3 to treat masseter hypertrophy. A total of 411 patients were treated by injection of BTX. Wide variability was found in the methods of injection and in the doses injected. Many trials concluded superiority of BTX injections over placebo for reducing TMD pain levels and improving maximum mouth opening; however, this was not universal. Conclusion: There is good scientific evidence to support the use of BTX injections for treatment of masseter hypertrophy and equivocal evidence for myogenous TMDs, but very little for TMJ articular disorders. Studies with improved methodologic design are needed to gain better insight into the utility and effectiveness of BTX injections for treating both myogenous and TMJ articular TMDs and to establish suitable protocols for treating different TMDs.

botulinum toxin; bruxism; myofascial; pain; temporomandibular disorders; temporomandibular joint

1. Ohrbach R, Bair E, Fillingim RB, et al. Clinical orofacial charac-teristics associated with risk of first-onset TMD: The OPPERA prospective cohort study. J Pain 2013;14(12 suppl):T33–T50.

2. The National Academies of Sciences, Engineering, and Medicine. Temporomandibular Disorders: Priorities for Research and Care. Washington, DC: The National Academies Press, 2020.

3. Schiffman E, Ohrbach R, Truelove E, et al. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for clinical and research applications: Recommendations of the International RDC/TMD Consortium Network and Orofacial Pain Special Interest Group. J Oral Facial Pain 2014;28:6–27.

4. Bouloux G, Koslin MG, Ness G, Shafer D. Temporomandibular joint surgery. J Oral Maxillofac Surg 2017;75(8S)e195–e223.

5. Guarda-Nardini L, Manfredini D, Berrone S, Frerronato G. Total temporomandibular joint prosthesis as a surgical option for severe mouth opening restriction, A case report of a bilateral intervention. Reumatismo 2007;59:322–327.

6. Foster KA, Bigalke H, Aoki KR. Botulinum neurotoxin - from laboratory to bedside. Neurotox Res 2006;9:133–140.

7. Dressler D. Therapeutically relevant features of botulinum toxin drugs. Toxicon 2020;175:64–68.

8. Dressler D, Benecke R. Pharmacology of therapeutic botuli-num toxin preparations. Disabil Rehabil 2007;29:1761–1768.

9. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotox 2005;26:785–793.

10. Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: Implications for migraine therapy. Headache 2004;44:35–42; discussion 42–33.

11. Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE. Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int 2008;101:366–370.

12. Cui M, Khanijou S, Rubino J Aoki KR. Subcutaneous adminis-tration of botulinun toxin A reduces formain-induced pain. Pain 2004;107:125–133.

13. Kharatmal SB, Singh JN, Sharma SS. Voltage-gated sodium channels as therapeutic targets for treatment of painful diabetic neuropathy. Min Rev Med Chem 2015;15:1134–1147.

14. Matak I, Riederer P, Lackovic´ Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int 2012;61:236–239.

15. Safarpour Y, Jabbari B. Botulinum toxin treatment of pain syndromes -an evidence based review. Toxicon 2018;147:120–128.

16. Thambar S, Kulkarni S, Armstrong S, Nikolorakos D. Botulinum toxin in the management of temporomandibular disorders: A systematic review. Br J Oral Maxillofac Surg 2020;58:508–519.

17. Chen YW, Chiu YW, Chen CY, Chuang SK. Botulinum toxin therapy for temporomandibular joint disorders: A systematic review of randomized controlled trials. Int J Oral Maxillofac Surg 2015;44:1018–1026.

18. Patel J, Cardoso JA, Mehta S. A systematic review of botulinum toxin in the management of patients with temporomandibular disorders and bruxism. Br Dent J 2019;226:667–672.

19. Machado D, Martimbianco ALC, Bussadori SK, Pacheco RL, Riera R, Santos EM. Botulinum toxin type A for painful temporomandibular disorders: Systematic review and meta-analysis. J Pain 2020;21:281–293.

20. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. J Clin Epidemiol 2009;62:1006–1012.

21. Sackett DL, Strauss SE, Richardson WS, Rosenberg W, Haynes RB. Evidence-Based Medicine: How to Practice and Teach EBM, ed 2. Edinburgh: Churchill Livingstone, 2000.

22. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?Control Clin Trials 1996;17:1–12.

23. Lee DH, Jin SP, Cho S, et al. RimabotulinumtoxinB versus OnabotulinumtoxinA in the treatment of masseter hypertro-phy: A 24-week double-blind randomized splitface study. Dermatology 2013;226:227–232.

24. Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain 2002;99:465–473.

25. Ernberg M, Hedenberg-Magnusson B, List T, Svensson P. Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: A randomized, controlled, double-blind multicenter study. Pain 2011;152:1988–1996.

26. Guarda-Nardini L, Manfredini D, Salamone M, Salmaso L, Tonello S, Ferronato G. Efficacy of botulinum toxin in treating myofascial pain in bruxers: A controlled placebo pilot study. Cranio 2008;26:126–135.

27. Guarda-Nardini L, Stecco A, Stecco C, Masiero S, Manfredini D. Myofascial pain of the jaw muscles: Comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique. Cranio 2012;30:95–102.

28. von Lindern JJ, Niederhagen B, Bergé S, Appel T. Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg 2003;61:774–778.

29. Kurtoglu C, Gur OH, Kurkcu M, Sertdemir Y, Guler-Uysal F, Uysal H. Effect of botulinum toxin-A in myofascial pain patients with or without functional disc displacement. J Oral Maxillofac Surg 2008;66:1644–1651.

30. Patel AA, Lerner MZ, Blitzer A. IncobotulinumtoxinA injection for temporomandibular joint disorder. Ann Otol Rhinol Laryngol 2017;126:328–333.

31. Altaweel AA, Elsayed SA, Baiomy AABA, Abdelsadek SE, Hyder AA. Extraoral versus intraoral botulinum toxin type A injection for management of temporomandibular joint disc displacement with reduction. J Craniofac Surg 2019;30:2149–2153.

32. Kütük SG, Özkan Y, Kütük M, Özdas¸ T. Comparison of the efficacies of dry needling and Botox methods in the treatment of myofascial pain syndrome affecting the temporomandibular joint. J Craniofac Surg 2019;30:1556–1559.

33. Cahlin BJ, Lindberg C, Dahlström L. Cerebral palsy and bruxism: Effects of botulinum toxin injections-A randomized controlled trial. Clin Exp Dent Res 2019;5:460–468.

34. Jadhao VA, Lokhande N, Habbu SG, Sewane S, Dongare S, Goyal N. Efficacy of botulinum toxin in treating myofascial pain and occlusal force characteristics of masticatory muscles in bruxism. Indian J Dent Res 2017;28:493–497.

35. De Carli BM, Magro AK, Souza-Silva BN, et al. The effect of laser and botulinum toxin in the treatment of myofascial pain and mouth opening: A randomized clinical trial. J Photochem Photobiol 2016;159:120–123.

36. De la Torre Canales G, Alvarez-Pinzon N, Muñoz-Lora VRM, et al. Efficacy and safety of botulinum toxin type A on persistent myofascial pain: A randomized clinical trial. Toxins (Basel) 2020;12:395.

37. Pihut ME, Margielewicz J, Kijak E, Wis´niewska G. Evaluation of articular disc loading in the temporomandibular joints after prosthetic and pharmacological treatment in model studies. Adv Clin Exp Med 2017;26:455–460.

38. Shandilya S, Mohanty S, Sharma P, Chaudhary Z, Kohli S, Kumar RD. Effect of preoperative intramuscular injection of botulinum toxin A on pain and mouth opening after surgical intervention in temporomandibular joint ankylosis cases: A controlled clinical trial. J Oral Maxillofac Surg 2020;78:916–926.

39. Ondo WG, Simmons JH, Shahid MH, Hashem V, Hunter C, Jankovic J. Onabotulinum toxin-A injections for sleep bruxism: A double-blind, placebo-controlled study. Neurology 2018;90:e559–e564.

40. Lee SJ, McCall WD Jr, Kim YK, Chung SC, Chung JW. Effect of botulinum toxin injection on nocturnal bruxism: A randomized controlled trial. Am J Phys Med Rehabil 2010;89:16–23.

41. Shim YJ, Lee MK, Kato T, Park HU, Heo K, Kim ST. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxism patients: A polysomnographic evaluation. J Clin Sleep Med 2014;10:291–298.

42. Shim YJ, Lee HJ, Park KJ, Kim HT, Hong IH, Kim ST. Botulinum toxin therapy for managing sleep bruxism: A randomized and placebo- controlled trial. Toxins 2020;12:168.

43. Zhang LD, Liu Q, Zou DR, Yu LF. Occlusal force characteristics of masseteric muscles after intramuscular injection of botulinum toxin A(BTX - A)for treatment of temporomandibular disorder. Br J Oral Maxillofac Surg 2016;54:736–740.

44. Kaya DI, Ataoglu H. Botulinum toxin treatment of temporomandibular joint pain in patients with bruxism: A prospective and randomized clinical study. Niger J Clin Pract 2021;24:412–417.

45. Lee JH, Park JH, Lee SK, et al. Efficacy and safety of inco-botulinum toxin A in periocular rhytides and masseter hyper-trophy: Side-by-side comparison with onabotulinum toxin A. J Dermatol Treat 2014;25:326–330.

46. Wei J, Xu H, Dong J, Li Q, Dai C. Prolonging the duration of masseter muscle reduction by adjusting the masticatory move-ments after the treatment of masseter muscle hypertrophy with botulinum toxin type A injection. Dermatol Surg 2015;41(suppl 1):s101–s109.

47. Khenioui H, Houvenagel E, Catanzariti JF, Guyot MA, Agnani O, Donze C. Usefulness of intraarticular botulinum injections: A systematic review. Joint Bone Spine 2016;83:149–154.

48. Arendt-Nielsen L, Jiang GL, DeGryse R, Turkel CC. Intraarticular onabotulinumtoxinA [sic] in osteoarthritis knee pain: Effect on human mechanistic pain biomarkers and clinical pain. Scand J Rheumatol 2017;46:303–316.

49. Lobbezoo F, Ahlberg J, Raphael KG, et al. International consensus on the assessment of bruxism: Report of a work in progress. J Oral Rehabil 2018;45:837–844.

50. Manfredini D, Winocur E, Guarda-Nardini L, Paesani D, Lobbezoo F. Epidemiology of bruxism in adults: A systematic review of the literature. J Orofac Pain 2013;27:99–110.

51. Manfredini D, Serra-Negra J, Carboncini F, Lobbezoo F. Current concepts of bruxism. Int J Prosthodont 2017;30:437–438.