Therapeutic Uses and Efficacy of Botulinum Toxin in Orofacial Medicine: From the Standpoint of Dental Professionals

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 46728

Special Issue Editors


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Guest Editor
Department of Oral and Maxillofacial Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
Interests: movement disorders; oromandibular dystonia; botulinum toxin therapy; orofacial pain; temporomandibular disorders; oral dyskinesia; neurophysiology; sleep apnea syndrome

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Guest Editor
Department of Odontology, University of Copenhagen, DK-2200 Copenhagen, Denmark
Interests: dentistry; neuromuscular disorders; electromyography; muscle physiology; muscle contraction; motor learning and motor control; biomechanics; muscle function; neuromuscular physiology; botulinum toxins

Special Issue Information

Dear Colleagues,

Increasing amounts of data show that the injection of botulinum toxin is an effective and safe treatment for various diseases in the stomatognathic system, such as oromandibular dystonia, bruxism, temporomandibular disorders, and trigeminal neuralgia. Botulinum toxin has mainly been studied by neurologists; however, dental care workers are much more familiar with the stomatognathic region than neurologists, and can administer injections in the region more professionally. Collaboration or a multidisciplinary team approach between neurologists and dental professionals will make diagnosis and treatment more secure and safer. Dental care workers should be more interested in this promising therapy, and we believe that cooperation between medical and dental professionals is important for that purpose. This Special Issue aims to discuss botulinum toxin therapy for various diseases in the oral region and its effects, especially from the standpoint of dental professionals.

Dr. Kazuya Yoshida
Prof. Dr. Merete Bakke
Guest Editors

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Keywords

  • botulinum toxin
  • botulinum toxin therapy
  • oromandibular dystonia
  • bruxism
  • movement disorder
  • multidisciplinary team approach
  • orofacial pain
  • temporomandibular disorders
  • neurophysiology
  • masticatory muscle

Published Papers (11 papers)

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Editorial

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5 pages, 215 KiB  
Editorial
Therapeutic Uses and Efficacy of Botulinum Toxin in Orofacial Medicine: A Dental Perspective
by Kazuya Yoshida and Merete Bakke
Toxins 2024, 16(5), 220; https://doi.org/10.3390/toxins16050220 - 10 May 2024
Viewed by 615
Abstract
Botulinum neurotoxin (BoNT) is the exotoxin of Clostridium botulinum, a Gram-positive, spore-forming bacterium [...] Full article

Research

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9 pages, 631 KiB  
Article
Long-Term Effects of a Single Application of Botulinum Toxin Type A in Temporomandibular Myofascial Pain Patients: A Controlled Clinical Trial
by Giancarlo De la Torre Canales, Mariana Barbosa Câmara-Souza, Rodrigo Lorenzi Poluha, Olívia Maria Costa de Figueredo, Bryanne Brissian de Souza Nobre, Malin Ernberg, Paulo César Rodrigues Conti and Célia Marisa Rizzatti-Barbosa
Toxins 2022, 14(11), 741; https://doi.org/10.3390/toxins14110741 - 29 Oct 2022
Cited by 8 | Viewed by 2922
Abstract
This study assessed the long-term effects of botulinum toxin type A (BoNT-A) in subjective pain, pain sensibility, and muscle thickness in persistent myofascial temporomandibular-disorder pain (MFP-TMD) patients. Fourteen female subjects with persistent MFP received BoNT-A treatment with different doses (10U-25U for temporalis muscle [...] Read more.
This study assessed the long-term effects of botulinum toxin type A (BoNT-A) in subjective pain, pain sensibility, and muscle thickness in persistent myofascial temporomandibular-disorder pain (MFP-TMD) patients. Fourteen female subjects with persistent MFP received BoNT-A treatment with different doses (10U-25U for temporalis muscle and 30U-75U for masseter muscle). The treatment was injected bilaterally in the masseter and anterior temporalis muscles in a single session. Clinical measurements included: self-perceived pain (VAS), pain sensibility (PPT), and muscles thickness (ultrasonography). Follow-up occurred 1, 3, 6, and 72 months after treatment for VAS and PPT and 1, 3, and 72 months for ultrasonography. For statistical analysis, the Friedman test with the Bonferroni test for multiple comparisons as a post hoc test was used for non-parametric repeated measures comparisons among the evaluation times. A 5% probability level was considered significant in all tests. VAS values presented a significant decrease throughout the study (p < 0.05). Regarding PPT values, a significant increase was found when comparing baseline data with post-treatment follow-ups (p < 0.05), and even though a significant decrease was found in muscle thickness when baseline values were compared with the 1- and 3-months assessments, no differences were found when compared with the 72 months follow-up (p > 0.05). A single injection of BoNT-A presents long-term effects in reducing pain in persistent MFP-TMD patients, and a reversibility of adverse effects on masticatory-muscle thickness. Full article
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16 pages, 7616 KiB  
Article
Effects of Botulinum Toxin Therapy on Health-Related Quality of Life Evaluated by the Oromandibular Dystonia Rating Scale
by Kazuya Yoshida
Toxins 2022, 14(10), 656; https://doi.org/10.3390/toxins14100656 - 22 Sep 2022
Cited by 4 | Viewed by 4584
Abstract
Oromandibular dystonia (OMD) refers to a focal dystonia in the stomatognathic system. Health-related quality of life (HRQoL) in isolated dystonia is associated with non-motor symptoms such as depression, anxiety, and pain, as well as motor symptoms. To evaluate HRQoL in patients with OMD, [...] Read more.
Oromandibular dystonia (OMD) refers to a focal dystonia in the stomatognathic system. Health-related quality of life (HRQoL) in isolated dystonia is associated with non-motor symptoms such as depression, anxiety, and pain, as well as motor symptoms. To evaluate HRQoL in patients with OMD, the therapeutic effects of botulinum neurotoxin (BoNT) therapy were assessed using a recently developed and validated comprehensive measurement tool called the Oromandibular Dystonia Rating Scale (OMDRS). Altogether, 408 patients (jaw closing dystonia, n = 223; tongue (lingual) dystonia, n = 86; jaw opening dystonia, n = 50; jaw deviation dystonia, n = 23; jaw protrusion dystonia, n = 13; and lip (labial) dystonia, n = 13) were evaluated at baseline and after the end of BoNT therapy or in a stable status. The total OMDRS score reduced significantly from 149.1 to 57.6 (p < 0.001). Mean improvement was 63.1%. All examiner-rated subscales (severity, disability, and pain) and patient-rated questionnaire scores (general, eating, speech, cosmetic, social/family life, sleep, annoyance, mood, and psychosocial function) were significantly lower at the endpoint than at baseline (p < 0.001). The BoNT injection had a highly positive impact on patient HRQoL, and the OMDRS could evaluate both motor phenomena and non-motor symptoms. Full article
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13 pages, 1522 KiB  
Article
Effect of Botulinum Toxin Injection on EMG Activity and Bite Force in Masticatory Muscle Disorder: A Randomized Clinical Trial
by Victoria Sitnikova, Antti Kämppi, Olli Teronen and Pentti Kemppainen
Toxins 2022, 14(8), 545; https://doi.org/10.3390/toxins14080545 - 10 Aug 2022
Cited by 5 | Viewed by 2475
Abstract
Botulinum toxin type A (BoNT-A) is increasingly used in treating masticatory muscle pain disorder; however, safe doses and reinjection intervals still need to be established. The purpose of this randomized clinical trial was to evaluate the degree and duration of the impairment of [...] Read more.
Botulinum toxin type A (BoNT-A) is increasingly used in treating masticatory muscle pain disorder; however, safe doses and reinjection intervals still need to be established. The purpose of this randomized clinical trial was to evaluate the degree and duration of the impairment of masticatory muscle performance. Fifty-seven subjects were randomly divided into two groups: one of which received BoNT-A first (n = 28) while the other received saline first (n = 29), with the cross-over being in week 16, and a total follow-up period of 32 weeks. A total dose of 50 U of BoNT-A was injected in the masseter and temporal muscles bilaterally. Electromyographic (EMG) activity and bite forces were assessed. A significant reduction in EMG activity was observed up to week 18 (p ≤ 001), with total recovery at week 33. A significant reduction in maximum bite force was observed up to week 11 (p ≤ 005), with total recovery at week 25. In conclusion, when treating masticatory muscle pain disorder with 50 U of BoNT-A, a reinjection interval of 33 weeks can be considered safe since the recovery of muscle function occurs by that time. Full article
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9 pages, 290 KiB  
Article
Efficacy of Botulinum Toxin Type-A I in the Improvement of Mandibular Motion and Muscle Sensibility in Myofascial Pain TMD Subjects: A Randomized Controlled Trial
by Giancarlo De la Torre Canales, Rodrigo Lorenzi Poluha, Natalia Alvarez Pinzón, Bruno Rodrigues Da Silva, Andre Mariz Almeida, Malin Ernberg, Ana Cristina Manso, Leonardo Rigoldi Bonjardim and Célia Marisa Rizzatti-Barbosa
Toxins 2022, 14(7), 441; https://doi.org/10.3390/toxins14070441 - 29 Jun 2022
Cited by 11 | Viewed by 3169
Abstract
This study assessed the effects of botulinum toxin type A (BoNT-A) in mandibular range of motion and muscle tenderness to palpation in persistent myofascial pain (MFP) patients (ReBEC RBR-2d4vvv). Eighty consecutive female subjects with persistent MFP, were randomly divided into four groups ( [...] Read more.
This study assessed the effects of botulinum toxin type A (BoNT-A) in mandibular range of motion and muscle tenderness to palpation in persistent myofascial pain (MFP) patients (ReBEC RBR-2d4vvv). Eighty consecutive female subjects with persistent MFP, were randomly divided into four groups (n = 20): three BoNT-A groups with different doses and a saline solution group (placebo control group). Treatments were injected bilaterally in the masseter and anterior temporalis muscle in a single session. Clinical measurements of mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral excursions. Palpation tests were performed bilaterally in the masseter and temporalis muscle. Follow-up occurred 28 and 180 days after treatment. For the statistical analysis the Mann–Whitney U-test with Bonferroni correction was used for groups comparisons. Regardless of dose, all parameters of mandibular range of motion significantly improved after 180 days in all BoNT-A groups, compared with the control group. Palpation pain over the masseter and temporalis muscles were significantly reduced in all BoNT-A groups regardless of dose, compared with the control group, after 28 and 180 days of treatment. Independent of doses, BoNT-A improved mandibular range of motion and muscle tenderness to palpation in persistent MFP patients. Full article

Review

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19 pages, 4922 KiB  
Review
Cosmetic Treatment Using Botulinum Toxin in the Oral and Maxillofacial Area: A Narrative Review of Esthetic Techniques
by Sung Ok Hong
Toxins 2023, 15(2), 82; https://doi.org/10.3390/toxins15020082 - 17 Jan 2023
Cited by 9 | Viewed by 14055
Abstract
Botulinum toxin (BoNT) is an anaerobic rod-shaped-neurotoxin produced by Clostridium botulinum, that has both therapeutic and lethal applications. BoNT injection is the most popular cosmetic procedure worldwide with various applications. Patients with dynamic wrinkles in areas such as the glabella, forehead, peri-orbital lines, [...] Read more.
Botulinum toxin (BoNT) is an anaerobic rod-shaped-neurotoxin produced by Clostridium botulinum, that has both therapeutic and lethal applications. BoNT injection is the most popular cosmetic procedure worldwide with various applications. Patients with dynamic wrinkles in areas such as the glabella, forehead, peri-orbital lines, nasal rhytides, and perioral rhytides are indicated. Excessive contraction of muscles or hyperactivity of specific muscles such as bulky masseters, cobble stone chins, gummy smiles, asymmetric smiles, and depressed mouth corners can achieve esthetic results by targeting the precise muscles. Patients with hypertrophic submandibular glands and parotid glands can also benefit esthetically. There are several FDA-approved BoNTs (obabotuli-numtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, letibotulinumtoxinA, prabotulinumtox-inA, daxibotulinumtoxinA, rimbotulinumtoxinB) and novel BoNTs on the market. This paper is a narrative review of the consensus statements of expert practitioners and various literature on the injection points and techniques, highlighting both the Asian and Caucasian population separately. This paper can serve as a practical illustrative guide and reference for optimal, safe injection areas and effective doses for application of BoNT in the face and oral and maxillofacial area. The history of BoNT indications, contraindications, and complications, and the merits of ultrasonography (US)-assisted injections are also discussed. Full article
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14 pages, 954 KiB  
Review
Neurophysiological Basis of Deep Brain Stimulation and Botulinum Neurotoxin Injection for Treating Oromandibular Dystonia
by Hitoshi Maezawa, Masayuki Hirata and Kazuya Yoshida
Toxins 2022, 14(11), 751; https://doi.org/10.3390/toxins14110751 - 2 Nov 2022
Viewed by 2915
Abstract
Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with [...] Read more.
Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with high temporal resolution. Previous studies with EEG and MEG have revealed that movements in the stomatognathic system are regulated by the bilateral central cortex. Recently, in addition to the standard therapy of botulinum neurotoxin (BoNT) injection into the affected muscles, bilateral deep brain stimulation (DBS) has been applied for the treatment of OMD. However, some patients’ OMD symptoms do not improve sufficiently after DBS, and they require additional BoNT therapy. In this review, we provide an overview of the unique central spatiotemporal processing mechanisms in these regions in the bilateral cortex using EEG and MEG, as they relate to the sensorimotor functions of the stomatognathic system. Increased knowledge regarding the neurophysiological underpinnings of the stomatognathic system will improve our understanding of OMD and other movement disorders, as well as aid the development of potential novel approaches such as combination treatment with BoNT injection and DBS or non-invasive cortical current stimulation therapies. Full article
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10 pages, 649 KiB  
Review
Botulinum Toxin, a Drug with Potential Interest for Dentists—An Introduction
by Merete Bakke
Toxins 2022, 14(10), 667; https://doi.org/10.3390/toxins14100667 - 25 Sep 2022
Cited by 3 | Viewed by 1912
Abstract
The review is an introduction to medical, non-cosmetic treatments with botulinum neurotoxin (BoNT) in the orofacial region. It focuses on the current most common, best-documented and safest indications of interest for dentists in terms of dystonia and sialorrhea. These conditions are recommended to [...] Read more.
The review is an introduction to medical, non-cosmetic treatments with botulinum neurotoxin (BoNT) in the orofacial region. It focuses on the current most common, best-documented and safest indications of interest for dentists in terms of dystonia and sialorrhea. These conditions are recommended to start with and suitable to gain better skill and experience with BoNT. The introduction also stresses the importance of correct diagnostics based on interdisciplinary cooperation, precise targeting of the injections, measurements of treatment effect, and control of the oral health with regard to side effects. Full article
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8 pages, 1830 KiB  
Review
Botulinum Toxin—A Current Place in the Treatment of Chronic Migraine and Other Primary Headaches
by Katarzyna Kępczyńska and Izabela Domitrz
Toxins 2022, 14(9), 619; https://doi.org/10.3390/toxins14090619 - 5 Sep 2022
Cited by 9 | Viewed by 7700
Abstract
Headaches are a very common condition that most people will experience many times during their lives. This article presents the primary headaches, which are a large group of diseases where the headache is not a symptom of another known disease. Tension-type headache affects [...] Read more.
Headaches are a very common condition that most people will experience many times during their lives. This article presents the primary headaches, which are a large group of diseases where the headache is not a symptom of another known disease. Tension-type headache affects approximately 80% of the general population, and the prevalence of migraine is estimated at 10–12%. Clinical data and experience to date have demonstrated that botulinum toxin may be an effective prophylactic treatment for chronic headache types. It has been used in neurology for the treatment of dystonia and blepharospasm. Now it has been approved to treat chronic migraine and has been shown to confer significant benefit in refractory cases. Based on clinical experience botulinum toxin has also been tried in other headache disorders. While it is intuitively attractive to think that due to its effect on pain by sensory modulation, there may also be efficacy in its use in chronic tension-type headache and cluster headache, so far, there is little evidence to support this. Botulinum toxin is effective in pain control through its interaction with the SNARE complex, which inhibits the release of neurotransmitters, such as glutamate, substance P and calcitonin gene-related peptide. OnabotulinumtoxinA is effective not only in headache frequency and pain intensity but in other parameters, including quality of life. Full article
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Other

13 pages, 1027 KiB  
Systematic Review
Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review
by Matteo Val, Robert Delcanho, Marco Ferrari, Luca Guarda Nardini and Daniele Manfredini
Toxins 2023, 15(9), 541; https://doi.org/10.3390/toxins15090541 - 1 Sep 2023
Cited by 1 | Viewed by 2345
Abstract
Background: The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP). Methods: A comprehensive literature search was conducted using Medline, Web of Science, [...] Read more.
Background: The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP). Methods: A comprehensive literature search was conducted using Medline, Web of Science, and the Cochrane Library databases. Only randomized clinical trials (RCT) published between 2003 and the end of June 2023, investigating the use of BTX to treat NP, were selected. PICO guidelines were used to select and tabulate the articles. Results: A total of 6 RCTs were selected. Five articles used BTX injections to treat classical trigeminal neuralgia, and one to treat post-herpetic neuralgia. A total of 795 patients received BTX injections. The selected studies utilised different doses and methods of injections and doses. All the selected studies concluded superiority of BTX injections over placebo for reducing pain levels, and 5 out 6 of them highlighted an improvement in the patient’s quality of life. Most of the studies reported transient and mild side effects. Conclusion: There is evidence of the efficacy of BTX injections in orofacial pain management. However, improved study protocols are required to provide direction for the clinical use of BTX to treat various orofacial neuropathic pain disorders. Full article
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7 pages, 959 KiB  
Case Report
Tardive Oromandibular Dystonia Induced by Trazodone: A Clinical Case and Management from the Perspective of the Dental Specialist
by Nicolás P. Skarmeta, Giannina C. Katzmann, Constanza Valdés, Dominique Gaedechens and Francisca C. Montini
Toxins 2022, 14(10), 680; https://doi.org/10.3390/toxins14100680 - 30 Sep 2022
Cited by 2 | Viewed by 2579
Abstract
Background: Tardive Oromandibular Dystonia is an iatrogenic drug-induced movement form of extrapyramidal symptoms associated primarily with chronic consumption of dopamine receptor blocking agents. Tardive symptoms attributable to selective serotonin reuptake inhibitors antidepressants are far less prevalent. Clinical Case: The authors will present a [...] Read more.
Background: Tardive Oromandibular Dystonia is an iatrogenic drug-induced movement form of extrapyramidal symptoms associated primarily with chronic consumption of dopamine receptor blocking agents. Tardive symptoms attributable to selective serotonin reuptake inhibitors antidepressants are far less prevalent. Clinical Case: The authors will present a clinical case and management, from the dental specialist perspective, of a 55-year-old female patient who developed tardive oromandibular dystonia induced by Trazodone prescribed for sleep insomnia. Conclusions: Trazodone-induced oromandibular dystonia is extremely rare. Early identification and assessment of tardive symptoms are imperative for successful treatment. Trazodone should be prescribed with caution in patients taking other medications with the potential to cause tardive syndromes. Full article
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