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Clinical Oral Investigations
Published in: Clinical Oral Investigations 9/2019

01-09-2019 | Craniomandibular Dysfunction and Stress | Review

Botulinum toxin type A applications for masticatory myofascial pain and trigeminal neuralgia: what is the evidence regarding adverse effects?

Authors: Giancarlo De la Torre Canales, Rodrigo Lorenzi Poluha, Victor Muñoz Lora, Dyna Mara Araújo Oliveira Ferreira, Juliana Stuginski-Barbosa, Leonardo Rigoldi Bonjardim, Altair Antoninha Del Bel Cury, Paulo César Rodrigues Conti

Published in: Clinical Oral Investigations | Issue 9/2019

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Abstract

Objectives

The objective of the study was to conduct a systematic review of literature assessing botulinum toxin type A (BoNT-A) safety and adverse effects in the treatment of myofascial pain (MFP) and trigeminal neuralgia (TN).

Materials and methods

The search for articles by two specific researchers involved the PubMed, EMBASE, Web of Science, and Scopus databases. Specific terms were used, and no publication time and language restrictions were applied. Clinical trials that investigated the effects of BoNT-A among participants with myofascial pain in masticatory muscles or trigeminal neuralgia were considered eligible for this systematic review. Data for each study were extracted and analyzed according to a PICO-like structured reading.

Results

The search strategy provided 436 citations. After analysis, 16 citations were included, seven for MFP and nine for TN. In all studies, BoNT-A was well tolerated and improved pain. The most common adverse effects were temporary regional weakness, tenderness over the injection sites, and minor discomfort during chewing. Most studies reported a spontaneous resolution of adverse effect.

Conclusions

It can be concluded that BoNT-A treatment is well tolerated, since minor adverse effects were the most frequently reported; however, it is recommended that future studies aim to assess the safety and possible adverse effects of multiples applications or high doses of this treatment.

Clinical relevance

BoNT-A has been increasingly diffused in dentistry, being used for the management of masticatory myofascial pain and trigeminal neuralgia. Nonetheless, there is no consensus about its efficacy and adverse effects that could occur when this treatment is applied.
Appendix
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Literature
1.
Pellett S, Yaksh TL, Ramachandran R (2015) Current status and future directions of botulinum neurotoxins for targeting pain processing. Toxins (Basel) 7:4519–4563CrossRef
2.
Thenganatt MA, Fahn S (2012) Botulinum toxin for the treatment of movement disorders. Curr Neurol Neurosci Rep 12:399–409CrossRefPubMed
3.
Colhado OCG, Boeing M, Ortega LB (2009) Botulinum toxin in pain treatment. Braz J Anesthesiol 59:366–381CrossRef
4.
Dressler D, Adib Saheri F, Reis Barbosa E (2005) Botulinum toxin: mechanisms of action. Arq Neuropsiquiatr 63:180–185CrossRefPubMed
5.
6.
Lora VRMM, Clemente-Napimoga JT, Abdalla HB, Macedo CG, de la Canales Torre G, Barbosa CMR (2017) Botulinum toxin type A reduces inflammatory hypernociception induced by arthritis in the temporomadibular joint of rats. Toxicon 129:52–57CrossRefPubMed
7.
Matak I, Tékus V, Bölcskei K, Lacković Z, Helyes Z (2017) Involvement of substance P in the antinociceptive effect of botulinum toxin type A: evidence from knockout mice. Neuroscience 358:137–145CrossRefPubMed
8.
Wu C-J, Lian Y-J, Zheng Y-K, Zhang H-F, Chen Y, Xie N-C, Wang LJ (2012) Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia 32:443–450CrossRefPubMed
9.
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice ASC, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14:162–173CrossRefPubMedPubMedCentral
10.
Ranoux D, Attal N, Morain F, Bouhassira D (2008) Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 64:274–283CrossRefPubMed
11.
De la Torre Canales G, Câmara-Souza MB, do Amaral CF, Garcia RCMR, Manfredini D (2017) Is there enough evidence to use botulinum toxin injections for bruxism management? A systematic literature review. Clin Oral Investig
12.
Zhang H, Lian Y, Ma Y, Chen Y, He C, Xie N et al (2014) Two doses of botulinum toxin type a for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial. J Headache Pain 15:1–6CrossRef
13.
Zúñiga C, Piedimonte F, Díaz S, Micheli F (2013) Acute treatment of trigeminal neuralgia with onabotulinum toxin A. Clin Neuropharmacol 36:146–150CrossRefPubMed
14.
Bohluli B, Motamedi MHK, Bagheri SC, Bayat M, Lassemi E, Navi F, Moharamnejad N (2011) Use of botulinum toxin A for drug-refractory trigeminal neuralgia: preliminary report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111:47–50CrossRefPubMed
15.
Morra ME, Elgebaly A, Elmaraezy A, Khalil AM, Altibi AM, Vu TL, Mostafa MR, Huy NT, Hirayama K (2016 Dec) Therapeutic efficacy and safety of botulinum toxin A therapy in trigeminal neuralgia: a systematic review and meta-analysis of randomized controlled trials. J Headache Pain 17(1):63CrossRefPubMedPubMedCentral
16.
Hu Y, Guan X, Fan L, Li M, Liao Y, Nie Z, Jin L (2013) Therapeutic efficacy and safety of botulinum toxin type A in trigeminal neuralgia: a systematic review. J Headache Pain 14:72CrossRefPubMedPubMedCentral
17.
Safarpour Y, Jabbari B (2018) Botulinum toxin treatment of pain syndromes –an evidence-based review. Toxicon. 147:120–128CrossRefPubMed
18.
Soares A, Andriolo RB, Atallah AN, da Silva EM (2014) Botulinum toxin for myofascial pain syndromes in adults. Cochrane Database Syst Rev (7):CD007533
19.
Khalifeh M, Mehta K, Varguise N, Suarez-Durall P, Enciso R (2016) Botulinum toxin type A for the treatment of head and neck chronic myofascial pain syndrome: a systematic review and meta-analysis. J Am Dent Assoc 147(12):959–973CrossRefPubMed
20.
Turton K, Chaddock JA, Acharya KR (2002) Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem Sci 27:552–558CrossRefPubMed
21.
Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM (2005) Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol 53:407–415CrossRefPubMed
22.
Kun-Darbois JD, Libouban H, Chappard D (2015) Botulinum toxin in masticatory muscles of the adult rat induces bone loss at the condyle and alveolar regions of the mandible associated with a bone proliferation at a muscle enthesis. Bone 77:75–82CrossRefPubMed
23.
Kim BW, Park GH, Yun WJ, Rho NK, Jang KA, Won CH, Chang SE, Chung SJ, Lee MW (2014) Adverse events associated with botulinum toxin injection: a multidepartment, retrospective study of 5310 treatments administered to 1819 patients. J Dermatol Treat 25:331–336CrossRef
24.
Rafferty KL, Liu ZJ, Ye W, Navarrete AL, Nguyen TT, Salamati A, Herring SW (2012) Botulinum toxin in masticatory muscles: short- and long-term effects on muscle, bone, and craniofacial function in adult rabbits. Bone 50:651–662CrossRefPubMed
25.
Raphael KG, Tadinada A, Bradshaw JM, Janal MN, Sirois DA, Chan KC, Lurie AG (2014) Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study. J Oral Rehabil 41(8):555–563CrossRefPubMed
26.
Lee HJ, Kim SJ, Lee KJ, Yu HS, Baik HS (2017) Repeated injections of botulinum toxin into the masseter muscle induce bony changes in human adults: a longitudinal study. Korean J Orthod 47(4):222–228CrossRefPubMedPubMedCentral
27.
Ho KY, Tan KH (2007) Botulinum toxin A for myofascial trigger point injection: a qualitative systematic review. Eur J Pain 11(5):519–527CrossRefPubMed
28.
Nixdorf DR, Heo G, Major PW (2002) Randomized controlled trial of botulinum toxin A for chronic myogenous orofacial pain. Pain. 99(3):465–473CrossRefPubMed
29.
Khawaja SN, Scrivani SJ, Holland N, Keith DA (2017) Effectiveness, safety, and predictors of response to botulinum toxin type a in refractory masticatory myalgia: a retrospective study. J Oral Maxillofac Surg 75(11):2307–2315CrossRefPubMed
30.
Kurtoglu C, Gur OH, Kurkcu M, Sertdemir Y, Guler-Uysal F, Uysal H (2008) Effect of botulinum toxin- A in myofascial pain patients with or without functional disc displacement. J Oral Maxillofac Surg 66(8):1644–1651CrossRefPubMed
31.
Guarda-Nardini L, Manfredini D, Salamone M, Salmaso L, Tonello S, Ferronato G (2008) Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study. Cranio. 26(2):126–135CrossRefPubMed
32.
Abboud WA, Hassin-Baer S, Joachim M, Givol N, Yahalom R (2017) Localized myofascial pain responds better than referring myofascial pain to botulinum toxin injections. Int J Oral Maxillofac Surg 46(11):1417–1423CrossRefPubMed
33.
Ernberg M, Hedenberg-Magnusson B, List T, Svensson P (2011) Efficacy of botulinum toxin type A for treatment of persistent myofascial TMD pain: a randomized, controlled, double-blind multicenter study. Pain. 152(9):1988–1996CrossRefPubMed
34.
Guarda-Nardini L, Stecco A, Stecco C, Masiero S, Manfredini D (2012) Myofascial pain of the jaw muscles: comparison of short-term effectiveness of botulinum toxin injections and fascial manipulation technique. Cranio. 30(2):95–102CrossRefPubMed
35.
Piovesan EJ, Teive HG, Kowacs PA, Della Coletta MV, Werneck LC, Silberstein SD (2005) An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 65(8):1306–1308CrossRefPubMed
36.
Zhang H, Lian Y, Ma Y, Chen Y, He C, Xie N, Wu C. Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia: observation of therapeutic effect from a randomized, double-blind, placebo-controlled trial. J Headache Pain. 2014;15:65
37.
Türk Börü Ü, Duman A, Bölük C, Coşkun Duman S, Taşdemir M (2017) Botulinum toxin in the treatment of trigeminal neuralgia: 6-month follow-up. Medicine (Baltimore) 96(39):e8133CrossRef
38.
Caldera MC, Senanayake SJ, Perera SP, Perera NN, Gamage R, Gooneratne IK (2018) Efficacy of botulinum toxin type an in trigeminal neuralgia in a South Asian Cohort. J Neurosci Rural Pract 9(1):100–105CrossRefPubMedPubMedCentral
39.
Liu J, Xu YY, Zhang AL, Luo WF (2018) Efficacy and safety of botulinum toxin type a in treating patients of advanced age with idiopathic trigeminal neuralgia. Pain Res Manag 7365148:5
40.
Wu CJ, Lian YJ, Zheng YK, Zhang HF, Chen Y, Xie NC, Wang LJ (2012) Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia. 32(6):443–450CrossRefPubMed
41.
Shehata HS, El-Tamawy MS, Shalaby NM, Ramzy G (2013) Botulinum toxin-type A: could it be an effective treatment option in intractable trigeminal neuralgia? J Headache Pain. 14:92CrossRefPubMedPubMedCentral
42.
Zhang H, Lian Y, Xie N, Chen C, Zheng Y (2017) Single-dose botulinum toxin type a compared with repeated-dose for treatment of trigeminal neuralgia: a pilot study. J Headache Pain 18(1):81CrossRefPubMedPubMedCentral
43.
Ramirez-Castaneda J, Jankovic J, Comella C, Dashtipour K, Fernandez HH, Mari Z (2013) Diffusion, spread and migration of botulinum toxin. Mov Disord 28(13):1775–1783CrossRefPubMed
44.
Kim KS, Byun YS, Kim YJ, Kim ST (2009) Muscle weakness after repeated injection of botulinum toxin type A evaluated according to bite force measurement of human masseter muscle. Dermatol Surg 35(12):1902–1906CrossRefPubMed
45.
Park HU, Kim BI, Kang SM, Kim ST, Choi JH, Ahn HJ (2013) Changes in masticatory function after injection of botulinum toxin type A to masticatory muscles. J Oral Rehabil 40(12):916–922CrossRefPubMed
46.
Tsai CY, Lin YC, Su B, Yang LY, Chiu WC (2012) Masseter muscle fibre changes following reduction of masticatory function. Int J Oral Maxillofac Surg 41(3):394–399CrossRefPubMed
47.
Fortuna R, Vaz MA, Youssef AR, Longino D, Herzog W (2011) Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox). J Biomech 44(1):39–44CrossRefPubMed
48.
Gedrange T, Gredes T, Spassov A, Mai R, Kuhn DU, Dominiak M, Kunert-Keil C (2013) Histological changes and changes in the myosin mRNA content of the porcine masticatory muscles after masseter treatment with botulinum toxin A. Clin Oral Investig 17(3):887–896CrossRefPubMed
49.
Raadsheer MC, van Eijden TM, van Ginkel FC, Prahl-Andersen B (1999) Contribution of jaw muscle size and craniofacial morphology to human bite force magnitude. J Dent Res 78(1):31–42CrossRefPubMed
50.
Matthys T, Ho Dang HA, Rafferty KL, Herring SW (2015) Bone and cartilage changes in rabbit mandibular condyles after 1 injection of botulinum toxin. Am J Orthod Dentofac Orthop 148(6):999–1009CrossRef
Metadata
Title
Botulinum toxin type A applications for masticatory myofascial pain and trigeminal neuralgia: what is the evidence regarding adverse effects?
Authors
Giancarlo De la Torre Canales
Rodrigo Lorenzi Poluha
Victor Muñoz Lora
Dyna Mara Araújo Oliveira Ferreira
Juliana Stuginski-Barbosa
Leonardo Rigoldi Bonjardim
Altair Antoninha Del Bel Cury
Paulo César Rodrigues Conti
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 9/2019
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-019-03026-4

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