Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0433604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2842 (Electronic) Linking ISSN: 0305182X NLM ISO Abbreviation: J Oral Rehabil Subsets: MEDLINE

Original Publication: Oxford, Blackwell Scientific Publications.

Botulinum Toxins, Type A*/therapeutic use ; Temporomandibular Joint Disorders*/drug therapy; Humans ; Randomized Controlled Trials as Topic ; Pain/drug therapy ; Treatment Outcome

Background: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear.
Objective: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD.
Methods: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model.
Results: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (μV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo.
Conclusions: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.
(© 2023 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Kapos FP, Exposto FG, Oyarzo JF, Durham J. Temporomandibular disorders: a review of current concepts in aetiology, diagnosis and management. Oral Surg. 2020;13(4):321‐334. doi:10.1111/ors.12473.
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 Headache. 2014;28(1):6‐27. doi:10.11607/jop.1151.
Mor N, Tang C, Blitzer A. Temporomandibular myofacial pain treated with botulinum toxin injection. Toxins. 2015;7(8):2791‐2800. doi:10.3390/toxins7082791.
Tjakkes GHE, Reinders JJ, Tenvergert EM, Stegenga B. TMD pain: the effect on health related quality of life and the influence of pain duration. Health Qual Life Outcomes. 2010;8:46. doi:10.1186/1477-7525-8-46.
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(3–4):281‐293. doi:10.1016/j.jpain.2019.08.011.
Luvisetto S. Botulinum neurotoxins in central nervous system: an overview from animal models to human therapy. Toxins. 2021;13(11):751. doi:10.3390/toxins13110751.
Thambar S, Kulkarni S, Armstrong S, Nikolarakos D. Botulinum toxin in the management of temporomandibular disorders: a systematic review. Br J Oral Maxillofac Surg. 2020;58(5):508‐519. doi:10.1016/j.bjoms.2020.02.007.
Cruse B, Dharmadasa T, White E, et al. Efficacy of botulinum toxin type a in the targeted treatment of sleep bruxism: a double‐blind, randomised, placebo‐controlled, cross‐over study. BMJ Neurol Open. 2022;4(2):e000328. doi:10.1136/bmjno-2022-000328.
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. 2020;12(6):395. doi:10.3390/toxins12060395.
De la Torre Canales G, Câmara‐Souza MB, Poluha RL, et al. Long‐term effects of a single application of botulinum toxin type a in temporomandibular myofascial pain patients: a controlled clinical trial. Toxins. 2022;14(11):741. doi:10.3390/toxins14110741.
De la Torre Canales G, Mb CS, Rl P, et al. Botulinum toxin type a and acupuncture for masticatory myofascial pain: a randomized clinical trial. J Appl Oral Sci. 2021;29:29. doi:10.1590/1678-7757-2020-1035.
De la Torre Canales G, Poluha RL, Pinzón NA, et al. Efficacy of botulinum toxin type‐a in the improvement of mandibular motion and muscle sensibility in myofascial pain TMD subjects: a randomized controlled trial. Toxins. 2022;14(7):441. doi:10.3390/toxins14070441.
De la Torre Canales G, Poluha RL, Alvarez Pinzón YN, et al. Effects of botulinum toxin type a on the psychosocial features of myofascial pain TMD subjects: a randomized controlled trial. J Oral Facial Pain Headache. 2021;35(4):288‐296. doi:10.11607/ofph.2917.
Montes‐Carmona JF, Gonzalez‐Perez LM, Infante‐Cossio P. Treatment of localized and referred masticatory myofascial pain with botulinum toxin injection. Toxins. 2020;13(1):6. doi:10.3390/toxins13010006.
Rezazadeh F, Esnaashari N, Azad A, Emad S. The effects of botulinum toxin a injection on the lateral pterygoid muscle in patients with a painful temporomandibular joint click: a randomized clinical trial study. BMC Oral Health. 2022;22(1):217. doi:10.1186/s12903-022-02220-3.
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(3):168. doi:10.3390/toxins12030168.
Sitnikova V, Kämppi A, Teronen O, Kemppainen P. Effect of botulinum toxin injection on EMG activity and bite force in masticatory muscle disorder: a randomized clinical trial. Toxins. 2022;14(8):545. doi:10.3390/toxins14080545.
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71.
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi:10.1136/bmj.l4898.
The Cochrane Collaboration. Cochrane. 2020. Published online 2020. Accessed February 19, 2023. https://www.cochrane.org/.
Higgins J, Thomas J, Chandler M, Li T, Page M, Welch V. Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). Cochrane. 2022. Accessed February 19, 2023. https://training.cochrane.org/handbook.
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(9):1988‐1996. doi:10.1016/j.pain.2011.03.036.
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(2):126‐135. doi:10.1179/crn.2008.017.
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(5):493‐497. doi:10.4103/ijdr.IJDR_125_17.
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(8):1644‐1651. doi:10.1016/j.joms.2008.03.008.
Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin a for chronic myogenous orofacial pain. Pain. 2002;99(3):465‐473. doi:10.1016/S0304-3959(02)00240-3.
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(7):e559‐e564. doi:10.1212/WNL.0000000000004951.
Patel AA, Lerner MZ, Blitzer A. IncobotulinumtoxinA injection for temporomandibular joint disorder. Ann Otol Rhinol Laryngol. 2017;126(4):328‐333. doi:10.1177/0003489417693013.
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(7):774‐778. doi:10.1016/s0278-2391(03)00153-8.
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(7):736‐740. doi:10.1016/j.bjoms.2016.04.008.
Ramos‐Herrada RM, Arriola‐Guillén LE, Atoche‐Socola KJ, Bellini‐Pereira SA, Castillo AAD. Effects of botulinum toxin in patients with myofascial pain related to temporomandibular joint disorders: a systematic review. Dent Med Probl. 2022;59(2):271‐280. doi:10.17219/dmp/145759.
Matak I, Bölcskei K, Bach‐Rojecky L, Helyes Z. Mechanisms of botulinum toxin type a action on pain. Toxins. 2019;11(8):459. doi:10.3390/toxins11080459.
Spiegel LL, Ostrem JL, Bledsoe IO. FDA approvals and consensus guidelines for botulinum toxins in the treatment of dystonia. Toxins. 2020;12(5):332. doi:10.3390/toxins12050332.

Keywords: bite force; botulinum toxins type a; masticatory muscles; pain; temporomandibular joint disorders; treatment outcome

EC 3.4.24.69 (Botulinum Toxins, Type A)

Date Created: 20231228 Date Completed: 20240409 Latest Revision: 20240409

20240409

10.1111/joor.13648

38151884