Hindawi Pain Research and Management Volume 2017, Article ID 6264146, 5 pages https://doi.org/10.1155/2017/6264146 Research Article The Evaluation of the Clinical Effects of Botulinum Toxin on Nocturnal Bruxism Fatih Asutay,1 Yusuf Atalay,2 Hilal Asutay,3 and Ahmet Hüseyin Acar4 1Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Afyon Kocatepe University, Afyonkarahisar, Turkey 2Vefa Diş Polikliniği, Afyonkarahisar, Turkey 3Uzman DentaClinic, Bursa, Turkey 4Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Bezmialem Vakıf University, İstanbul, Turkey Correspondence should be addressed to Fatih Asutay; dt_asutay@hotmail.com Received 29 March 2017; Accepted 21 May 2017; Published 5 July 2017 Academic Editor: Lucindo Quintans Copyright © 2017 Fatih Asutay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. Nocturnal bruxism can be managed by botulinum toxin (Botox) in patients who have not responded to conservative treatment. The aim of this study was to evaluate the efficacy of botulinum toxin A (BTXA) in the treatment of nocturnal bruxism. Material andMethods.The retrospective study comprised 25 female patients, aged 23–55 years (mean 35.84±8.41 years). All patients received a single injection of BTXA in the right and left masseters. Evaluation was made by Visual Analogue Scale (VAS) values, complaint duration, onset of effect, and duration of effectiveness. Results. BTXA produced significant improvements in pain scores. Only 2 adverse events (8%) were recorded. Conclusion. BTX-A is effective in the treatment of nocturnal bruxism. 1. Introduction and glabellar wrinkles for BTXA and cervical dystonia for BTXB. Nocturnal bruxism (NB) is defined as abnormal maxillo- BTXA has been used in the treatment of cosmetic and mandibular activity during sleep, characterized by grinding noncosmetic conditions such as tremor, hemifacial spasm, and clenching of the teeth [1, 2]. NB can lead to wear on temporomandibular joint dysfunction, bruxism, masticatory the teeth, dental prostheses/implant failure, tooth sensitivity, myalgias, sialorrhea, hyperhidrosis, and headache [7]. pain in the teeth, jaw, masticatory muscle, and temporo- Botox injections are directly applied into the masseter mandibular joint (TMJ), neck pains and headache, periodon- and temporalis muscles to relax these muscles. The clinical tal disease, oral or facial pain, and potentially tooth loss [3, 4]. effects are typically seen on the first to third days after the These problems can be associated with the unconscious and injection, followed by one to two weeks of maximum effect, intense contractions of the temporal and masseter muscles and the typical duration of the effect is three to four months during sleep [5]. There are various treatment techniques [8]. for the management of NB such as oral splint, behavioral In two comprehensive review studies, Tinastepe et al. [1] approaches, and medications (muscle relaxants, botulinum and Manfredini et al. [2] suggested that there is not enough toxin) but none is widely accepted [4]. evidence to use botulinum injection in the treatment of Botulinum toxin (Botox) is an exotoxin produced by the bruxism. The purpose of the present study was to investigate bacteriumClostridiumbotulinum, which blocks acetylcholine the potential performance of BTXA on nocturnal bruxism release from cholinergic nerve endings into the neuromuscu- and to share this clinical experience. lar junction, thereby causing inactivity of muscles or glands [6]. Botulinumneurotoxin typesA (BTXA) andB (BTXB) are 2. Materials and Methods approved by theUnited States Food andDrugAdministration (FDA) including cervical dystonia, severe primary axillary In the period 2014-2015, a retrospective data analysis was hyperhidrosis, strabismus, blepharospasm, hemifacial spasm, made of the data of 25 female patients who underwent 2 Pain Research and Management onabotulinum toxin A (Botox, Allergan, Inc., Irvine, CA, 12.24 ± 2.02 days, and the time that the loss of effectiveness USA) injections into the masseter muscle for clinically diag- started was 4.76 ± 1.01months (Table 3). nosed nocturnal bruxism. The patients enrolled in the study The differences between two-week–four-month and one- had all failed to respond to conservative treatment. Exclu- month–three-month postoperative pain values were not sta- sion criteria were temporomandibular disorders, pregnancy, tistically significant. However, differences between all other active drug use, and psychological therapy. times were statistically significant (Table 4). For evaluation of postoperative pain, Visual Analogue Scale (VAS) forms were completed by the patients scoring 4. Discussion the degree of pain between 0 (absence of pain) and 10 (maximum pain) before the injection and then at 2 weeks, In the present study, there were significant differences in 1 month, 3 months, 4 months, and 6 months after the injec- reduction of pain and bruxism activity. tion. Van Zandijcke andMarchau [9] used botulinum toxin for The following data were recorded for all patients: max- the first time in the treatment of bruxism of a young woman imum mouth opening changes, duration of the complaint with a brain injury, and a marked reduction was observed. before the injection, muscle weakness before injection, the Thereafter, botulinum toxin was used for the treatment of time the first effectswere seen, the timewhen the effectiveness bruxism with different origins such as cranial-cervical dysto- started to be lost, and difficulty experienced in speaking, nia [10], Huntington’s disease [11], autism [12], and amphet- swallowing, or chewing. amine addiction [13]. This study was based on routine service documents of To date, only BTXA and BTXB serotypes have been NB patients. However, permission to analyse the data was approved by the US Food and Drug Administration (FDA) sought from the management of the Dentistry Hospital of for clinical use including cervical dystonia, severe primary Afyon Kocatepe University. All procedures followed were axillary hyperhidrosis, strabismus, blepharospasm, hemifa- in accordance with the ethical standards of the committee cial spasm, and glabellar wrinkles for BTXA and cervical responsible for human experimentation (institutional and dystonia for BTXB. national) andwith theHelsinkiDeclaration of 1975, as revised Lang [14] reported that BTXA showed better and longer in 2008. Written informed consent was obtained from all the pain relief than BTXB. Moreover, BTXA had fewer side- study participants. effects than BTXB [14]. In our clinic, BTXA has been safely used for the treatment of bruxism, masseteric hypertrophy, 2.1. Procedure. For all patients, 100 mouse units (MU) of and sialorrhea. onabotulinum toxin A (Botox, Allergan, Inc., Irvine, CA) Although the pathogenesis of bruxism remains unclear, were diluted in 2ml of saline. it is generally accepted that the etiology is multifactorial in In all patients, a dose of 20MU of BTXA was injected nature. The occurrence of nocturnal bruxism suggests that it into a singlemassetermuscle using a 0.5mL insulin syringe at may occur as a result of possible physical or psychological four points (5MU/site). The patient was requested to clench conditions (emotional stress, anxiety, aggressive and hyper- the masseter muscle, and the injections were applied to the active personality types, malocclusion, sleep problems such origin, insertion, anterior, and posterior parts of the mus- as sleep apnea, earache, headache, and tooth ache, the side- cle. effects of some psychiatric medications, etc.) [13, 15]. The treatment of myofascial pain can be difficult for 2.2. Statistical Analysis. Statistical analysis was performed both clinicians and patients because most of these disorders with the Statistical Package for the Social Science Program involve multiple components such as somatic, neurogenic, (version 20.0, SPSS Inc., Chicago, USA). Differences in indi- and psychogenic components. Moreover, it can be resistant vidual parameters were tested using the repeated measures to conventional medical or behavioral therapy. There is no test ANOVA and post hoc Friedman and Wilcoxon test for consensus on how the effects of Botox reduce pain. Some abnormally distributed variables (pain). A value of 𝑝 < 0.05 hypotheses have suggested changes in levels of muscle noci- was considered statistically significant. ceptor sensitizers, nonacetylcholine neurotransmitters, and acetylcholine at autonomic synapses [16–18] and decreased 3. Results motor neuron activity [19]. Nocturnal bruxism may lead to pain in the head, neck, Evaluation was made of the data of 25 female patients with a jaw, teeth, and temporomandibular joint (TMJ). However, mean age of 35.84 ± 8.41 years (range, 23–55 years). All the conservative treatments may be limited in the resolution study variables are shown in Tables 1 and 2. of this problem. In the past few years, the use of Botox One patient had pain in the injection points. No adverse therapy has become a promising source for the management effects or dry mouth (injection into parotid gland) was of myofascial pain [20]. The findings related to pain in the reported in any other patients. current study showed a significant difference before and There were no significant changes in respect of the after the injection, which is consistent with the findings of maximum mouth opening. Only 2 patients (8%) had no Sidebottom AJ et al. [21], Guarda-Nardini et al. [22], and Tan significant improvements in the pain scores after treatment. et al. [23]. The mean duration of the complaint before injection was In a study by Lee et al. [24], it was reported that BTXA 8.84 ± 4.57 years, the time that the effects were first seen was injection reduced the number of bruxism events during sleep Pain Research and Management 3 Table 1: The demographic data, pain scores, the time of the onset of the effect, the time of the onset of the loss of effect, and the duration of the complaint of all the patients. Patient Age VAS Scores Onset of effect (day) Onset of lose of effect (month) Duration of complaint (year) Pre-op 2.w 1.m 3.m 4.m 6.m 1 25 8 1 1 0 2 6 10 4 1 2 23 5 1 1 3 4 5 13 3 4 3 24 7 5 1 1 1 7 14 6 1 4 29 8 3 1 0 0 3 14 5 8 5 55 8 7 6 6 7 8 15 4 12 6 36 6 2 1 1 1 2 12 5,5 5 7 31 7 0 0 0 1 3 10 5 15 8 26 8 2 4 7 7 7 15 2,5 9 9 40 9 5 2 2 2 4 13 5 11 10 41 6 3 1 1 1 4 12 5 7 11 36 7 3 0 0 2 4 11 6 9 12 34 4 0 0 0 0 1 10 5 4 13 37 6 2 1 1 1 2 14 5 5 14 29 7 2 1 1 2 3 12 4,5 8 15 48 7 1 0 0 0 1 13 5,5 10 16 43 6 3 2 2 2 3 15 5 3 17 51 8 1 0 0 2 3 9 4 12 18 46 8 3 1 1 1 2 9 4 14 19 33 9 4 1 1 1 3 11 5 18 20 32 7 0 0 0 1 2 8 4 13 21 37 7 2 0 0 1 2 14 4 7 22 29 9 2 1 1 1 1 13 6 6 23 42 8 7 7 7 7 7 13 5 15 24 35 6 0 0 0 0 1 12 5,5 13 25 34 7 1 0 0 0 1 14 5 11 Abbreviations. VAS: Visual Analogue Scale, BTXA: Botulinum Toxin A, w: week, m: month. Table 2: The characteristics of the patients according to the pain [25]. In the present study, 20MU BTXA was injected into scores. each masseter muscle and positive results were reported. VAS Kesikburun et al. [26] reported a 21-year-old male patient with traumatic brain injury, whowas successfully treatedwith Before injection 7.12 ± 1.236 (4–9) BTXA for bruxism. According to our clinical experience, 2nd week 2.40 ± 1.979 (0–7) BTXA can be used safely for the treatment of bruxism. 1st month 1.28 ± 1.815 (0–7) The maximum mouth opening may be increased after 3rd month 1.40 ± 2.141 (0–7) injection of BTXA. Sidebottomet al. [21] andGuarda-Nardini 4th month 1.88 ± 2.128 (0–7) et al. [22] reported that the interincisal distance can be 6th month 3.40 ± 2.141 (1–8) induced with BTXA injection. However, the results of the current study do not match this conclusion. The differences may be due to most of the patients having no previous complaint of limited mouth opening or they may have been and it was therefore suggested that BTXA injection could due to the small sample size. be used as an effective treatment for nocturnal bruxism. The limitations of the present study include the small Similarly, Santamato et al. [25] reported that neck pain related sample size and that therewas no information about temporal to nocturnal bruxism can be treated with BTXA. In the study injection or difference between genders. by Santamato et al. [25], the dose of BTXA injected into each In conclusion, Botox therapy seems promising and bene- masseter muscle was 40MU and 25MU was injected into ficial in the treatment of nocturnal bruxism, although several each temporalis muscle. Moreover, electromyography was limiting factors such as high cost and the necessity for used to measure to the changes of masseter and temporalis repeated injections prevent its widespread use. When there muscle hyperactivities and VAS was used to measure to pain has been no response to conservative treatment methods, 4 Pain Research and Management Table 3: The characteristics of the patients according to age, onset of effect, onset of loss of effect, and duration of complaint. Age Onset of effect (day) Onset of loss of effect (month) Duration of complaint (year) Mean ± SD 35.84 ± 8.41 12.24 ± 2.02 4.76 ± 1.01 8.84 ± 4.57 Min–max 23–55 8–15 2–6 1–18 Table 4: Test statisticsa. aWilcoxon signed ranks test. bBased on positive ranks. cBased on negative ranks. vas2w-vaspi Vas1m-vaspi Vas3m-vaspi Vas4m-vaspi Vas6m-vaspi 𝑍 −4,390b −4,410b −4,395b −4,392b −4,124b Asymp.Sig. (2-tailed) ,000 ,000 ,000 ,000 ,000 vas1m-vas2w vas3m-vas2w Vas4m-vas2w vas6m-vas2w 𝑍 −3,257b −2,751b −1,629b −2,644c Asymp.Sig. (2-tailed) ,001 ,006 ,103 ,008 vas3m-vas1m vas4m-vas1m vas6m-vas1m vas4m-vas3m 𝑍 −,736c −2,656c −4,234c −2,762c Asymp.Sig. (2-tailed) ,461 ,008 ,000 ,006 vas6m-vas3m Vas6m-vas4m 𝑍 −4,148c −4,239c Asymp.Sig. (2-tailed) ,000 ,000 vaspi: VAS score at preinjection; vas2w: VAS score at 2 weeks (after injection); vas1m: VAS score in first month; vas3m: VAS score in third month; vas4m: VAS score in fourth month; vas6m: VAS score in sixth month. botulinum toxinmay be an alternative and effective treatment [4] K. Koyano, Y. Tsukiyama, R. Ichiki, and T. Kuwata, “Assessment for nocturnal bruxism and masticatory pain. Future studies of bruxism in the clinic,” Journal of Oral Rehabilitation, vol. 35, with a larger number of patients are required to confirm the no. 7, pp. 495–508, 2008. conclusions reached in the present study. [5] Y. J. Shim, M. K. Lee, T. Kato, H. U. Park, K. Heo, and S. T. Kim, “Effects of botulinum toxin on jaw motor events during sleep Consent in sleep bruxism patients: a polysomnographic evaluation,”Journal of Clinical Sleep Medicine, vol. 10, no. 3, pp. 291–298, Patient consent was obtained. 2014. [6] L. C. Sellin and S. Thesleff, “Pre- and post-synaptic actions of botulinum toxin at the rat neuromuscular junction.,” The Conflicts of Interest Journal of Physiology, vol. 317, no. 1, pp. 487–495, 1981. The authors declare that they have no conflicts of interest. [7] A. Blitzer and L. Sulica, “Botulinum toxin: basic science and clinical uses in otolaryngology,” Laryngoscope, vol. 111, no. 2, pp. 218–226, 2001. Acknowledgments [8] G. E. Borodic, M. Acquadro, and E. A. Johnson, “Botulinum Special thanks are due to Professor İsmet Doğan for his toxin therapy for pain and inflammatory disorders: mecha-nisms and therapeutic effects,”ExpertOpinion on Investigational support in the statistical analyses. Drugs, vol. 10, no. 8, pp. 1531–1544, 2001. [9] M. Van Zandijcke and M. M. Marchau, “Treatment of bruxism References with botulinum toxin injections,” Journal of Neurology Neuro- surgery and Psychiatry, vol. 53, no. 6, p. 530, 1990. [1] N. Tinastepe, B. B. Küçük, and K. Oral, “Botulinum toxin for [10] M. W. Watts, E.-K. Tan, and J. Jankovic, “Bruxism and cranial- the treatment of bruxism,” Cranio, vol. 33, no. 4, pp. 292–299, cervical dystonia: is there a relationship?” Cranio, vol. 17, no. 3, 2015. pp. 196–201, 1999. [2] D. Manfredini, J. Ahlberg, E. Winocur, and F. Lobbezoo, “Man- [11] M. C. Nash, R. B. Ferrell, M. A. Lombardo, and R. B. Williams, agement of sleep bruxism in adults: a qualitative systematic “Treatment of bruxism in Huntington’s disease with botulinum literature review,” Journal of Oral Rehabilitation, vol. 42, no. 11, toxin [2],” Journal ofNeuropsychiatry andClinicalNeurosciences, pp. 862–874, 2015. vol. 16, no. 3, pp. 381-382, 2004. [3] M. C. Carra, N. Huynh, and G. Lavigne, “Sleep bruxism: a [12] P. G. Monroy and M. A. Da Fonseca, “The use of botulinum comprehensive overview for the dental clinician interested in toxin-A in the treatment of severe bruxism in a patient with sleep medicine,” Dental Clinics of North America, vol. 56, no. 2, autism: a case report,” Special Care in Dentistry, vol. 26, no. 1, pp. 387–413, 2012. pp. 37–39, 2006. Pain Research and Management 5 [13] S.-J. See and E.-K. Tan, “Severe amphethamine-induced brux- ism: treatment with botulinum toxin,”Acta Neurologica Scandi- navica, vol. 107, no. 2, pp. 161–163, 2003. [14] A. M. Lang, “A preliminary comparison of the efficacy and tolerability of botulinum toxin serotypes A and B in the treatment of myofascial pain syndrome: a retrospective, open- label chart review,”ClinicalTherapeutics, vol. 25, no. 8, pp. 2268– 2278, 2003. [15] G. D. Klasser, N. Rei, andG. J. Lavigne, “Sleep bruxism etiology: the evolution of a changing paradigm,” Journal of the Canadian Dental Association, vol. 81, no. f2, 2015. [16] A. G. Hohmann and M. Herkenham, “Cannabinoid receptors undergo axonal flow in sensory nerves,” Neuroscience, vol. 92, no. 4, pp. 1171–1175, 1999. [17] A. Bengtsson, K. G. Henriksson, and J. Larsson, “Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia,”Arthritis &Rheumatism, vol. 29, no. 7, pp. 817–821, 1986. [18] A. H. Wheeler, “Myofascial pain disorders: theory to therapy,” Drugs, vol. 64, no. 1, pp. 45–62, 2004. [19] C. C. Donaldson, D. V. Nelson, and R. Schulz, “Disinhibition in the gamma motoneuron circuitry: a neglected mechanism for understanding myofascial pain syndromes?” Applied Psy- chophysiology Biofeedback, vol. 23, no. 1, pp. 43–59, 1998. [20] C. Kurtoglu, O.H.Gur,M. Kurkcu, Y. Sertdemir, F. Guler-Uysal, and H. Uysal, “Effect of botulinum toxin-A in myofascial pain patients with or without functional disc displacement,” Journal of Oral and Maxillofacial Surgery, vol. 66, no. 8, pp. 1644–1651, 2008. [21] A. J. Sidebottom, A. A. Patel, and J. Amin, “Botulinum injection for the management of myofascial pain in the masticatory muscles: a prospective outcome study,” British Journal of Oral and Maxillofacial Surgery, vol. 51, no. 3, pp. 199–205, 2013. [22] L. Guarda-Nardini, D. Manfredini, M. Salamone, L. Salmaso, S. Tonello, and G. Ferronato, “Efficacy of botulinum toxin in treating myofascial pain in bruxers: a controlled placebo pilot study,” Cranio, vol. 26, no. 2, pp. 126–135, 2008. [23] E.-K. Tan and J. Jankovic, “Treating severe bruxism with botulinum toxin,” Journal of the American Dental Association, vol. 131, no. 2, pp. 211–216, 2000. [24] S. J. Lee,W. D.McCall, Y. K. Kim, S. C. Chung, and J.W. Chung, “Effect of botulinum toxin injection on nocturnal bruxism: a randomized controlled trial,” American Journal of Physical Medicine and Rehabilitation, vol. 89, no. 1, pp. 16–23, 2010. [25] A. Santamato, F. Panza, D. Di Venere et al., “Effectiveness of botulinum toxin type A treatment of neck pain related to noc- turnal bruxism: a case report,” Journal of Chiropractic Medicine, vol. 9, no. 3, pp. 132–137, 2010. [26] S. Kesikburun, R. Alaca, B. Aras, I. Tuǧcu, and A. K. Tan, “Botulinum toxin injection for bruxism associated with brain injury: case report,” Journal of Rehabilitation Research and Development, vol. 51, no. 4, pp. 661–664, 2014. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of International Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at https://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Stem Cells Complementary and Journal of Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Mathematical Methods Behavioural AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014