|Year : 2016 | Volume
| Issue : 3 | Page : 166-170
Effect of botulinum Toxin-A in myofascial pain in temporomandibular disorders: A randomized, double-blinded, placebo-controlled study
Amit Gupta1, Anju Aggarwal2, Anurag Aggarwal3
1 Department of Dental and Maxillofacial Surgery, LHMC and SSKH, New Delhi, India
2 Department of Prosthodontics, ITS CDSR Dental College, Noida, Uttar Pradesh, India
3 Department of Neuroanaesthesia and Critical Care, Fortis Hospital, Noida, Uttar Pradesh, India
|Date of Web Publication||10-Jan-2017|
Department of Neuroanaesthesia and Critical Care, Fortis Hospital, Noida, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: The temporomandibular disorders (TMDs) include a heterogeneous group of clinical conditions affecting the stomatognathic system and its related structures. It is characterized by pain specific to the maxillofacial region, and these disorders are the main cause of chronic facial pain and disability. Management of TMDs is challenging due to the unknown etiology and complex anatomy of the temporomandibular joint region. Aim and Objectives: To evaluate the effect of botulinum toxin type-A (BTX-A) on pain and day to day functional and social activities of myofascial pain with or without TMDs, and to compare the effectiveness of BTX-A with a placebo group with the aid of EMG and a Behavioural Questionnaire. Materials and Methods: The study was done on 24 patients randomly divided into two groups and each group contains 12 participants. The study group showed a statistically significant decrease in the muscle activity after 14 days, and the patients responded that there was a significant reduction in the pain and improvement in their day-to-day functional as well as social activities after BTX-A treatment with 8 months follow-up. Conclusion: BTX-A has been proven to have positive desired effects on patients with TMDs.
Keywords: Botulinum toxin type-A, myofascial pain, temporomandibular disorders
|How to cite this article:|
Gupta A, Aggarwal A, Aggarwal A. Effect of botulinum Toxin-A in myofascial pain in temporomandibular disorders: A randomized, double-blinded, placebo-controlled study. Indian J Pain 2016;30:166-70
|How to cite this URL:|
Gupta A, Aggarwal A, Aggarwal A. Effect of botulinum Toxin-A in myofascial pain in temporomandibular disorders: A randomized, double-blinded, placebo-controlled study. Indian J Pain [serial online] 2016 [cited 2020 Jan 26];30:166-70. Available from: http://www.indianjpain.org/text.asp?2016/30/3/166/198013
| Introduction|| |
The temporomandibular disorders (TMDs) characterize a heterogeneous group of conditions involving the temporomandibular joint (TMJ), its associated structures, and its functions. TMJ disorders may be the result of primary or secondary degenerative changes within the joint resulting from or leading to muscular hyperfunction or parafunction. These disorders are the main cause of chronic facial pain and disability. 
It has characteristic clinical findings such as pain, joint sounds, and irregular or deviating jaw function.  It has been aptly demonstrated in various studies of TMJ disorders that by reducing the hyperfunction or parafunction of muscle of mastication appreciable relief from pain, and other symptoms can be achieved. ,,, The recent development intramuscular botulinum toxin type-A (BTX-A) in masticatory muscles is advocated in the management of TMJ disorders. ,,
The aim of the study is to evaluate the effect of BTX-A on pain and day-to-day functional and social activities of myofascial pain with or without TMDs and to compare the effectiveness of BTX-A with a placebo group.
Setting and design
This is a prospective, randomized control study conducted on patients visiting the department of oral and maxillofacial surgery, with diagnosis of TMDs. The study protocol was approved by the Local Ethics Committee.
| Materials and Methods|| |
A total of 24 patients were included in the study randomly divided into two groups: Study group and control group (12 patients in each group). All the patients were well informed about the procedure, and written informed consent obtained.
The inclusion criteria were patients with complaint of pain, restricted mouth opening, and clicking; patients despite conservative management not got relief from symptoms.
The exclusion criteria were age below 20 years or above 50 years, a history of allergic reactions, pregnancy, lactation, and immunocompromised patients.
The participants were evaluated at before and on day 14 and 28 after the BTX-A injection with the aid of electromyography (EMG) to assess the alteration in muscle activity and behavioral questionnaire to assess the reduction in pain and improvement in the day-to-day functional and social activities.
In this study, needle EMG (NEMG) recorder (Viking Quest, Germany) was used to record the right and left masseter and anterior temporal muscles. To determine the points of placing electrode, the participants were asked to bite down lightly on their teeth for a short time. After palpation of the origin and insertion of the masseter muscle, NEMG (Disposable Concentric Needle Electrode; VIASYS Healthcare, USA) was placed parallel to the long axis of the muscle at the equal distance from the origin and insertion of the muscle [Figure 1] and [Figure 2]. The anterior border of the anterior temporal muscle was determined by palpation, and the NEMG electrode was placed behind the frontal process of the zygomatic bone, 1.5-2 cm superiorly to the zygomatic arch, perpendicular to the sagittal plane [Figure 1] and [Figure 2].  The EMG records were taken simultaneously from the muscles. Muscle tonus was recorded for 5 s at rest position and then for 5 s at maximum clenching. Electromyographic studies were carried out on before initial treatment, 14 th , and 28 th day of injections, and readings were recorded.
|Figure 1: Line diagram showing botulinum toxin type-A injection points on the masseter and temporalis muscles along with various anatomical structures.|
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A customized behavior questionnaire was prepared for the patients enrolled in this study. The patients were asked to respond to nine sections which included 45 questions with respect to quality of life related to pain, mouth opening, social activities, and psychological status before the initial treatment and at the 1-month follow-up visit. Each section was scored on a scale of 0-4, and maximum score of all nine sections will be 36, the higher the score signifying more severe symptoms or a poorer level of functioning.
BTX-A injection was used for the study, and it was reconstituted according to standard recommendations. Whether the participant's complaint was unilateral or bilateral, injections were given bilaterally. The percutaneous route is preferred, and 10 units were deposited in 10 standardized points of the masseter and temporalis muscles [Figure 1],[Figure 2] and [Figure 3] that mean 3 points each in 2 masseter muscles and 2 points each in 2 temporalis muscles. On the masseter muscle, superior point was 0.5 cm below the tragal -chelion line, inferior point 1 cm above the inferior border of the mandible, and the middle point in between the above two mentioned points to prevent injury to the parotid duct, marginal mandibular branch, and buccal branch of the facial nerve, respectively.  On the temporalis muscle, anterior point was 1 cm behind the anterior border of the temporalis muscle, and the posterior point was 1 cm behind the anterior point to prevent the injury to branches of the superficial temporal artery and facial nerve. Adverse effects of Botox include allergic reactions, rash, itching, headache, difficulty swallowing, shortness of breath, nausea, diarrhea, weakness, injection site reactions including muscle weakness and bruising, flu symptoms, dizziness, drowsiness, and dry mouth were mentioned in literature. However, no signs of any kind of adverse reaction were noted in our study except local needle site reactions such as redness.
|Figure 3: Insertion of the needle and deposition of botulinum toxin type-A in the masseter muscle.|
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Descriptive statistics were calculated, and statistical intergroup comparison of the EMG readings and subjective scores from the questionnaires was performed with Student's t-test and compare the P value with level of significance.
| Results|| |
The results of our study were evaluated with the aids of EMG and behavioral questionnaire. The readings of EMG's and behavioral questionnaires were recorded before initial treatment and 14 th and 28 th day after the BTX-A/placebo injection. Clinically, none of the study/control group patients had reported with any postinjection complication during the study period except for one patient in the study group who complained of pain and numbness at the site of injection after 2 days. In the control group, no complaint was reported at all.
From the statistical analysis of data, the following results were obtained:
- The EMG results for the study group showed a statistically significant decrease in the muscles activity during rest and clenching between baseline (0 day) and 28 th day (P < 0.05), whereas in control group, an increase in the muscle activity for both masseter and temporalis muscles was noticed during the study period [Table 1]
- The behavioral questionnaire results for the study group showed a statistically significant relief from the pain. The patients responded that there was a significant improvement in their day-to-day functional and social activities after BTX-A treatment when compared with preprocedure behavioral questionnaire. Whereas in control group, no statistically significant reduction in the pain and improvement in the daily life activities was found [Figure 4].
|Figure 4: Intergroup comparison of mean behavior questionnaire scores before and after botulinum toxin type-A and placebo injections.|
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|Table 1: Intragroup comparison of EMG in various parameters with in the study group before and after BTX-A using t-test|
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| Discussion|| |
The TMDs include a heterogeneous group of clinical conditions affecting the stomatognathic system and its related structures. Management of TMDs is challenging for oral and maxillofacial surgeon due to the unknown etiology and complex anatomy of the TMJ region. Various authors have suggested several treatment modalities, which range from nonsurgical to surgical procedures, but none of the conventional techniques have been found to have achieved the desired results.  Thus, the recent development of minimally invasive BTX-A injection was advocated in the management of the TMDs with less adverse effect. 
The fate of the BTX-A used as an alternative treatment modality in refractory TMDs patients, whether it has been effective or not is an issue which is attracting a lot of debate.
BTX-A injection has recently become a popular treatment modality for cosmetic corrections, oromandibular dystonia, myofascial pain with or without TMDs, masseter hypertrophy, and migraine, etc. ,,, It is a safe and minimally invasive procedure that may be performed under local anesthesia, without sedation on an outpatient basis and its main purpose is to alter the muscular activity by inhibiting the release of acetylcholine at the motor nerve-end plates.
Randomized, double-blinded, placebo-control, and follow-up period has an important effect on the results of a clinical study. LeResche stated that these prospective studies affect the quality of evidence in clinical trials.  Our study was randomized, double-blinded, placebo-control study done on 24 patients with myofascial pain with or without functional disc displacement (12 in study group and 12 in control group) in the age group of 20-50 years. Thus, our study was in accordance with the considerations of LeResche, except for adequate final sample size. 
Freund et al.  stated that the effect of BTX-A is related to localization and dosage such as 25-50 U for the masseter and 5-25 U for the temporalis muscles. In previous studies, five different injection sites for each muscle were preferred, but in our study, total of 10 U of BTX-A was deposited in 10 standardized points on the masseter and temporalis muscles bilaterally; 30 MU for the masseter at three injections sites and 20 MU for the temporalis muscles at two injections sites were injected [Figure 1],[Figure 2] and [Figure 3]. The injections were given bilaterally in the muscles to avoid selection bias, and also by bilateral injections, muscles will have equal power otherwise there could be discrepancy in power leading to unequal weight loading of TMJ joints and poor outcome. Thus, the number of penetrations to the muscles and injury to the vital structures such as parotid duct, marginal mandibular branch of the facial nerve, and branches of the superficial temporal artery was kept to a minimum.
In the previous studies, BTX-A injection sites were not standardized, and toxin was deposited randomly on the thickest part of the muscle, ,,, but our study has standardized the injection sites thus having reported no adverse effect except for one patient who complained of pain and numbness over the right masseter muscle after 2 days of BTX-A injection which was temporary and resolved by itself after 1 week.
In our study, NEMG was used to evaluate the effect of BTX-A/placebo (isotonic saline) on muscle activity before and after the treatment. NEMG is the gold standard methodology for assessing the neurophysiologic characteristics of neuromuscular disease and in kinesiologic analysis of movement disorders.  Klasser and Okeson et al. and Pullman et al. concluded that surface EMG (SEMG) is substantially inferior to NEMG for the evaluation of patients with neuromuscular disorders, and they also stated that SEMG has limited spatial resolution that leads to more mechanical artifacts than NEMG. , Thus, our study was in accordance with the considerations of Okeson and Pullman et al. and showed that the significant alteration in the muscle activity during the study period with less mechanical artifacts.
Holmgren et al. and Abekura et al. reported the existence of asymmetric muscular activity at rest position in the muscles of TMDs patients.  Their results demonstrated that the masticatory muscles presented statistically different values in electrical activity when the muscles on the right were compared with those on the left. The asymmetric muscular activity seen in our study is in accordance with these studies.
Kurtoglu et al. and Freund and Schwartz used BTX-A for the treatment of TMD, and they had observed that reduced maximum voluntary clenching begins to decrease after 14 days and reverts to baseline levels in 8 weeks. ,,,, These findings are consistent with those of our study.
Pain is the most frequent and complex symptom of TMDs and is related to the articular and myofascial structures. Schwartz and Freund at eland von Lindern et al. stated that local injection of very small doses of BTX-A toxin into a muscle produces selective paralysis of muscle bundle , and therefore an individual muscle can be selectively weakened, thereby reducing pain, tenderness of the muscles directly, and decrease the inflammation in the articular structures indirectly. ,, The latter is achieved with the prolonged "joint sparing" effect of diminished loading secondary to the decrease ability of the musculature to the effect joint loading. These findings are consistent with those of our study.
In the study group, there was a statistically significant improvement in pain and psychological status after comparing behavioral questionnaires of baseline to day 14 (P < 0.001) and baseline to day 28 (P < 0.001). Whereas in the control group, no significant difference was evident over time during the study period. Tesch et al. stated that if pain had reduced, a positive change in psychological status was seen as in our study group. 
All study group participants had reported with improvement in mouth opening and clicking that could be because of reduction of pain directly and decreased inflammation in the articular structures indirectly.
In patients with myofascial pain with or without functional disc displacement, who cannot be treated effectively with conservative modalities, BTX-A can be injected into the masticatory muscle. The improvement in pain, daily activities, and psychological status was assessed by recording EMG and a behavioral questionnaire at the predetermined intervals postinjection of BTX-A. In our study, all the parameters had improved gradually with time, till the 6 th -month posttreatment period. Thus, it is logical to accept the effectiveness of BTX-A with this time-based correlation which means that repeated injections of BTX-A after every 6-8 th months might be required for long-term relief.
Our results are encouraging and have been promising, showing a significant improvement in symptoms after BTX-A injection into the masseter and temporalis muscles. Hence, we recommend BTX-A injection as an alternative treatment modality in those TMDs participants who cannot be treated effectively with conservative modalities. However, long-term studies with more number of patients and longer follow-up are required to affirmatively confirm the effect of BTX-A used in maxillofacial pain and TMDs.
| Conclusion|| |
BTX-A has been proven to have positive desired effects on patients with TMDs. Our study has further proven that injection BTX-A decreases the muscle activity in 14 days and reverts back to baseline after 8 weeks with improvement in pain and psychological status of the myofascial pain patients with or without disc displacement.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]