Efficacy of botulinum toxin for the management of orofacial pain and dysfunction : A Systematic review and Meta-analysis

Main Article Content

Suphanthaka Sairat
Somsak Mitrirattanakul
Ammarin Thakkinstian
Sasivimol Rattanasiri
Tassanee Tengrungsun
Touch Itthikul
Nattawut Unwanatham


Objective: Orofacial pain (OFP) are the conditions that affect quality of life, psychological and socioeconomic
status. The treatment goal is to reduce pain and function. The aim of this systematic review and meta analysis was to determine the efficacy of botulinum toxin (BTX) for reduce pain and restore normal function that compared with placebo, standard treatment, and/or active treatment in orofacial pain (OFP) patients.

Material and Methods: Electronic search for randomized controlled trial (RCT) was made until March 2017.
Search strategies and study selection was conducted following PRISMA guideline. Publications were assessed for risk-of-bias using the Cochrane Handbook. The outcomes were VAS score, MOA (mouth opening assessment), HD (headache day), and NDI (number of drug pills ingest). STATA was utilized to conduct direct meta-analysis.

Results: Eighteen RCT (946 patients) met the inclusion were divided into three groups for pooled outcomes.
In group 1, BTX-A subjects had a significantly lower VAS score when compared to the NSS group (pooled WMD= -1.81, 95% CI: -3.23 to - 0.39). In group 2, the BTX-A subjects had significantly lower HD than the NSS subjects (pooled WMD = -1.66 95% CI: -2.64 to -0.69), and a significantly lower NDI than the NSS subjects (pooled WMD = -2.51 95% CI: -4.42 to -0.60). In group 3, we could not analyze the outcome because there were only 2 studies in this group.
Discussion: BTX-A subjects showed significant pain relief in group 1, and the BTX-A subjects had significantly
lower HD and significantly lower NDI than the NSS subjects in group 2.

Conclusion: More rigorous design of trials should be carried out in future study to help the clinicians decisions.


Download data is not yet available.

Article Details

How to Cite
Sairat S, Mitrirattanakul S, Thakkinstian A, Rattanasiri S, Tengrungsun T, Itthikul T, Unwanatham N. Efficacy of botulinum toxin for the management of orofacial pain and dysfunction : A Systematic review and Meta-analysis. M Dent J [Internet]. 2020 Aug. 26 [cited 2023 Nov. 30];40(2):121-36. Available from: https://he02.tci-thaijo.org/index.php/mdentjournal/article/view/208852
Original articles


Reny DL, Gary DK, ditors. Orofacial Pain Guidelines for Assessment, Diagnosis, and Management Fifth Edition. 5th ed. Quintessence Publishing Co, Inc2013.

Macfarlane TV, Blinkhorn AS, Davies RM, Kincey J, Worthington HV. Oro-facial pain in the community: prevalence and associated impact. Community Dent Oral Epidemiol2002; 30: 52-60.

Lucchetti G, Peres MF. The prevalence of migraine and probable migraine in a Brazilian favela: results of a community survey. Headache2011; 51: 971-9.

Queiroz LP, Barea LM, Blank N. An epidemiological study of headache in Florianopolis, Brazil. Cephalalgia2006; 26: 122-7.

Zebenholzer K, Andree C, Lechner A, Broessner G, Lampl C, Luthringshausen G, et al. Prevalence, management and burden of episodic and chronic headaches--a cross-sectional multicentre study in eight Austrian headache centres. J Headache Pain2015; 16: 531.

Zebenigus M, Tekle-Haimanot R, Worku DK, Thomas H, Steiner TJ. The prevalence of primary headache disorders in Ethiopia. J Headache Pain 2016 ;17: 110.

Manandhar K, Risal A, Steiner TJ, Holen A, Linde M. The prevalence of primary headache disorders in Nepal: a nationwide population-based study. J Headache Pain 2015; 16: 95.

Domingues RB, Cezar PB, Schmidt Filho J, de Moraes Filho MN, Pinheiro MN, Marchiori JG, et al. Prevalence and impact of headache and migraine among Brazilian Tupiniquim natives. Arq Neuropsiquiatr2009; 67: 413-5.

Felicio AC, Bichuetti DB, Santos WA, Godeiro Junior Cde O, Marin LF, Carvalho Dde S. Epidemiology of primary and secondary headaches in a Brazilian tertiary-care center. Arq Neuropsiquiatr2006; 64: 41-4.

Herekar AA, Ahmad A, Uqaili UL, Ahmed B, Effendi J, Alvi SZ, et al. Primary headache disorders in the adult general population of Pakistan - a cross sectional nationwide prevalence survey. J Headache Pain2017; 18: 28.

Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and Burden of Migraine in the United States: Data From the American Migraine Study II. Headache2001; 41: 646-57.

Mbewe E, Zairemthiama P, Yeh HH, Paul R, Birbeck GL, Steiner TJ. The epidemiology of primary headache disorders in Zambia: a population-based door-to-door survey. J Headache Pain2015;16: 515.

Sipila K, Tolvanen M, Mitrirattanakul S, Sitthisomwong P, Jarvelin MR, Taanila A, et al. Orofacial pain and symptoms of temporomandibular disorders in Finnish and Thai populations. Acta Odontol Scand2015; 73: 330-5.

Allena M, Steiner TJ, Sances G, Carugno B, Balsamo F, Nappi G, et al. Impact of headache disorders in Italy and the public-health and policy implications: a population-based study within the Eurolight Project. J Headache Pain2015; 16: 100.

Dao TT, Lavigne GJ, Charbonneau A, Feine JS, Lund JP. The efficacy of oral splints in the treatment of myofascial pain of the jaw muscles: a controlled clinical trial. Pain1994; 56: 85-94.

van Grootel RJ, Buchner R, Wismeijer D, van der Glas HW. Towards an optimal therapy strategy for myogenous TMD, physiotherapy compared with occlusal splint therapy in an RCT with therapy-and-patient-specific treatment durations. BMC musculoskelet disord2017; 18: 76.

Ekberg EC, Vallon D, Nilner M. Occlusal appliance therapy in patients with temporomandibular disorders. A double-blind controlled study in a short-term perspective. Acta Odontol Scand1998; 56: 122-8.

Bendtsen L, Evers S, Linde M, Mitsikostas DD, Sandrini G, Schoenen J. EFNS guideline on the treatment of tension-type headache - Report of an EFNS task force. Eur J Neurol2010; 17: 1318-25.

Taylor JC, Brauer S, Espir ML. Long-term treatment of trigeminal neuralgia with carbamazepine. Postgrad Med J1981; 57: 16-8.

Dodick DW, Turkel CC, Degryse RE, Aurora SK, Silberstein SD, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache2010; 50: 921-36.

Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia2010; 30: 804-14.

Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, Degryse RE, et al. OnabotulinumtoxinA for treatment of chronic migraine: Pooled analyses of the 56-week PREEMPT clinical program. Headache2011; 51: 1358-73.

Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia2010; 30: 793-803.

Jackson JL, Kuriyama A, Hayashino Y. Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. Jama2012; 307: 1736-45.

Shuhendler AJ, Lee S, Siu M, Ondovcik S, Lam K, Alabdullatif A, et al. Efficacy of botulinum toxin type A for the prophylaxis of episodic migraine headaches: a meta-analysis of randomized, double-blind, placebo-controlled trials. Pharmacotherapy2009; 29: 784-91.

Shackleton T, Ram S, Black M, Ryder J, Clark GT, Enciso R. The efficacy of botulinum toxin for the treatment of trigeminal and postherpetic neuralgia: a systematic review with meta-analyses. Oral Surg Oral Med Oral Pathol Oral Radiol2016; 122: 61-71.

Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med2015; 162: 777-84.

Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ2011; 343: d5928.

Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ1997; 315: 629-34.

Al-Wayli H. Treatment of chronic pain associated with nocturnal bruxism with botulinum toxin. A prospective and randomized clinical study. J Clin Exp Dent2017; 9: e112-e7.

De Carli BM, Magro AK, Souza-Silva BN, Matos Fde S, De Carli JP, Paranhos LR, 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 B2016; 159: 120-3.

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. Pain2011; 152: 1988-96.

Freitag FG, Diamond S, Diamond M, Urban G. Botulinum Toxin Type A in the treatment of chronic migraine without medication overuse. Headache2008; 48: 201-9.

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. Cranio2008; 26: 126-35.

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. Cranio2012; 30: 95-102.

Magalhaes E, Menezes C, Cardeal M, Melo A. Botulinum toxin type A versus amitriptyline for the treatment of chronic daily migraine. Clin Neurol Neurosurg2010; 112: 463-6.

Nixdorf DR, Heo G, Major PW. Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain2002; 99: 465-73.

Ondo WG, Vuong KD, Derman HS. Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia2004; 24: 60-5.

Padberg M, de Bruijn SF, de Haan RJ, Tavy DL. Treatment of chronic tension-type headache with botulinum toxin: a double-blind, placebo-controlled clinical trial. Cephalalgia2004; 24: 675-80.

Rollnik JD, Tanneberger O, Schubert M, Schneider U, Dengler R. Treatment of tension-type headache with botulinum toxin type A: a double-blind, placebo-controlled study. Headache2000; 40: 300-5.

Schmitt WJ, Slowey E, Fravi N, Weber S, Burgunder JM. Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial. Headache2001; 41: 658-64.

Schulte-Mattler WJ, Krack P. Treatment of chronic tension-type headache with botulinum toxin A: a randomized, double-blind, placebo-controlled multicenter study. Pain2004; 109: 110-4.

Song JH, Zhang GB, Ding XD, Huang L, Hong Y, Chen HX. Efficacy of type a botulinum toxin injections and infrared polarized light on treating chronic migraine. Eur Rev Med Pharmacol Sci2015; 19: 1976-82.

Straube A, Empl M, Ceballos-Baumann A, Tolle T, Stefenelli U, Pfaffenrath V. Pericranial injection of botulinum toxin type A (Dysport) for tension-type headache - a multicentre, double-blind, randomized, placebo-controlled study. Eur J Neurol2008; 15: 205-13.

Wu CJ, Lian YJ, Zheng YK, Zhang HF, Chen Y, Xie NC, et al. Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia2012; 32: 443-50.

Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D. Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med2010; 11: 1827-33.

von Lindern JJ, Niederhagen B, Berge S, Appel T. Type A botulinum toxin in the treatment of chronic facial pain associated with masticatory hyperactivity. J Oral Maxillofac Surg2003; 61: 774-8.

Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Acad Emerg Med1998; 5: 1086-90.