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J Stomatol Oral Maxillofac Surg xxx (2018) xxx–xxx

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Original Article

The use of botulinum toxin-a in the treatment of muscular

temporomandibular joint disorders
A. Sipahi Calis a,*, Z. Colakoglu b, S. Gunbay a
a
Ege University School of Dentistry Oral Surgery Dept, Izmır, Turkey
b
Ege University School of Medicine Neurology Dept, Izmır, Turkey

A R T I C L E I N F O A B S T R A C T

Article history: Introduction: Botulinum toxin has been used mainly in the treatment of muscular temporomandibular
Received 25 November 2018 joint disorders (TMD) and hyperactivity of the masticatory muscles. It is used also as a therapeutic option
Accepted 4 February 2019 to relieve pain and help in functional recovery from dental, oral and maxillofacial surgery. The aim of our
study was to investigate the efficacy of botulinum toxin injection in the treatment of muscular TMD.
Keywords: Materials and methods: Of the 200 temporomandibular joint patients who applied for treatment,
botulinum toxin 25 patients with muscular dysfunction of the origin were included in the study. This patient group
temporomandibular joint
received drug, drug - physical therapy, occlusal splint therapy and botulinum toxin. These treatments
temporomandibular joint disorders
bruxiszm
were performed step by step. Botulinum toxin was applied, in accordance with reflex measurement in
pain electromyography guidelines to nine patients whose results were not success from the other treatments
had not been successful. Measurements were taken of bite force, pain and mouth openness.
Results: Sixteen patients were treated with drug-physical therapy-occlusal splint therapy, and
botulinum toxin treatment was found to be successful in the case of nine patients. No side effects
were observed at six months follow-up.
Conclusion: Botulinum toxin injection for the treatment of muscular temporomandibular joint disorder is
a viable treatment option in the case of patients who do not respond to conservative treatment methods.
C 2019 Elsevier Masson SAS. All rights reserved.

1. Introduction interventions to further surgical interventions [1–7]. Diet control,

The aim of treatment in temporomandibular joint disorders
(TMD) is to relieve symptoms and regain jaw movements. General
principles in the treatment of TMD are: correct diagnosis,
determination of etiological factors and removal of etiological
factors.
According to the American Academy of Orofacial Pain, TMDs are
classified into two groups: myogenous TMD, which is related more
to masticatory muscle disorders; and arthrogenous TMD, which is
related more to the temporomandibular joint (TMJ) itself [1]. A
wide range of factors are taken into consideration in the diagnosis
of muscular temporomandibular joint diseases, including: bruxism
during sleeping, jaw pain, morning headaches, orthodontic
treatment, trauma history, personal habits, diet, stress, and
gum-chewing frequency. Both physical examination and imaging
techniques are used in diagnosis. Various treatment modalities
have been suggested for TMD, from patient education to
pharmacological and psychological therapy and from non-invasive
* Corresponding author.
E-mail address: aysipahi@gmail.com (A. Sipahi Calis).
pain control, physiotherapy, warm compresses and occlusal splints
are non-pharmacological treatments for the the muscular tempo-
romandibular joint. Pharmacological treatments used are: anti-
inflammatory medications, muscle relaxants, analgesics, tricyclic
antidepressants (psychological treatment) and botulinum toxin.
Botulinum toxin (BTX) is an important factor for the mitigation
of muscle hyperactivity and pain in muscular temporomandibular
joint diseases. BTX is the exotoxin of a gram positive anaerobic
bacterium called Clostridium botulinum and has eight different
types (A, B, C1, C2, D, E, F, and G). BTX-A and BTX-B are clinically
applied to specific areas. The most commonly used BTX-A products
marketed worldwide are: BOTOX1 (Allergan, Inc, Irvine, CA, USA)
and Dysport1 (Ipsen Ltd, Maidenhead, Berkshire, UK); and, for
BTX-B: MYOBLOC1 (Elan Pharmaceuticals, Inc, South San Fran-
cisco, CA, USA). MYOBLOC1, unlike BTX-A, is sold in solution form
and is mainly used in neurology. BOTOX1 and Dysport1 come in
the form of a white powder and are used after dilution. Because
BOTOX1 is 50 to 100 times more effective than comparable doses
of Dysport1 and MYOBLOC1, it is advised to exercise caution when
deciding the dosage for this product during treatment.8 BTX-A is a
biological variant that temporarily inhibits the skeletal muscle.

https://doi.org/10.1016/j.jormas.2019.02.015
2468-7855/ C 2019 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Sipahi Calis A, et al. The use of botulinum toxin-a in the treatment of muscular temporomandibular
joint disorders. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.02.015
G Model
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It hinders activation of calcium channels in the nerve endings [1–
3,6,8–10]. BTX is also used for the treatment of focal dystonia,
strabismus, hemifacial spasm, dystonic tics, urinary sphincter
dissynergy, cerebral palsy, myofascial pain, headache, temporo-
mandibular joint disorders and reduction of hyperkinetic facial
lines [2,3,5,7–9,11].
The duration of action of BTX is long and it requires two to four
months for the regenerative processes to take effect. The initial
onset of the effect occurs two to three days after injection. The
therapeutic effect of BTX should be checked after two to three
weeks. Botulinum toxin gives rise to paresis when applied to
muscle tissue. The paresis level can be controlled by the amount of
BTX administered. The effect of BTX is limited to the target muscle
but three months is required for regenerate innervation. Side
effects of botulinum toxin are inevitable. These can be readily-
apparent side effects (e.g. flu-like symptoms) or not always
apparent (facultative). Local side effects (BTX-A may be diffused to
neighboring tissues from the target tissue) and systemic side
effects (BTX-A can be accidentally injected into the bloodstream)
are all categorized as facultative [12–15].
Organ damage is unlikely to occur. The targeting of muscle does
not cause necrotic or fibrotic changes. At very high doses, there
may be widespread weakness, fatigue, shortness of breath,
dysphagia, perspiration episodes and difficulty with accommoda-
tion.
To improve clinical success in the practice use of BTX-A in
temporomandibular joint diseases, these conditions need to be
met:
 the painful chewing muscles need to be correctly identified;
 there should be no evidence of general hyperactivity in the
masticatory muscles;
 the possibility of arthrogenic causes must be eliminated;
 the patient must show resistance to conservative treatments for
a period of at least 3 months;
 there must be no contra-indications to BTX-A treatment.
BTX is effective in relieving pain in cases of bruxism by reducing
local inflammation modulators. This leads to a resting position in
the muscles by reducing the contraction force in the resulting
muscle fibers’ contraction of inhibition. In bruxism treatment, BTX
is recommended for temporal, masseter and lateral pterygoid
muscles. Doses recommended for these are 10–25 units for
temporal muscle, 25–50 units for masseter muscle and 7.5–10
units for lateral pterygoid muscle [12,13,16].
The aim of our study was to investigate the efficacy of BTX in the
treatment of muscular temporomandibular joint disorders.
2. Material and method
Between September 2003 and March 2006, 200 patients with
temporomandibular joint disorders were admitted to the Depart-
ment of Oral Surgery, Faculty of Dentistry. Twenty-five patients
who were diagnosed as having muscular temporomandibular
disorders, in accordance with the Research Diagnostic Criteria for
Temporomandibular Disorders [17], were included in the study.
The study was carried out in the Dentistry Faculty’s Oral Surgery
Department and the Medical Faculty Neurology Department.
Approval for the study was granted by the Medical Faculty
Research Ethics Committee.
Inclusion criteria for the study:
 unsuccessful results from drug, physical therapy and occlusal
splint (3 months of conservative treatment resistance) [1–6,9];
 pregnancy test ( );
Please cite this article in press as: Sipahi Calis A, et al. The use of botulinum toxin-a in the treatment of muscular temporomandibular
joint disorders. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.02.015
 no systemic disease;
 no edentolous jaw.
3. Medication
Analgesic-anti-inflammatory (Lornoxicam, Xefo1 8 mg film
coated tablet, Abdi Abraham).
Muscle relaxants (Tizanidine HCl; Sirdalud (R) 2 mg tablet,
Novartis).
Antidepressant (Amitriptyline HCl; Laroxyl1 10 mg drage,
Roche).
In the first fifteen days, triple drug administration was
performed.
4. Medicine + Physical Therapy
Diathermy was applied to the troubled muscle area. In physical
therapy, Radarmed 650 Enraf Nonius B.V. was used. Microwave
warming was performed 10 times at 30 8C for 15 minutes in the
affected temporomandibular joint region. Physical therapy with
medication was carried out over the following 15 days.
An occlusal splint was used in combination with the drug
therapy, beginning at the end of the first month until the third
month. The occlusal splint was made in the upper jaw to raise the
occlusion to 2 mm thickness for a period of six months. Pre-
administration blood counts were performed on all patients.
A total of 16 patients from the 25 were healed by medication,
physical therapy and occlusal splint. These treatments were
applied step by step, in ascending order until one proved
successful. Nine patients (4 males, 5 females) who did not respond
to these treatments were selected to have BTX administered after
three months. Measurements were taken before and three weeks
after application (when the drug is at its most effective) for: bite
force (using a specially- designed force meter), pain (according to
the VAS scale), and mouth openness (millimetric calculation) for
the patients who were to be administered with Botulinum toxin
type A. Administration of the drug was carried out in line with
reflex measurement in electromyography guidelines [2,5,9]. A total
of 100 units of BTX type A were used on both sides of the face,
including the masseter muscle for 30 units and the temporal
muscle for 20 units [7,10]. Xerostomia, jaw weakness, difficulty
chewing and cosmetic side effects were checked.
Post-treatment follow-up was carried out for a period of six
months. The Chi-square test was used for statistical analysis.
5. Results
The biggest of the treatment groups (38%) (16 of the 25 patients)
was the drug-physical therapy-occlusal splint group (P < 0.05).
Sixteen (64%) of the 25 patients with myogenic temporoman-
dibular joint dysfunction received drug-physical therapy-occlusal
splint. Drug-physiotherapy-occlusal splint-botox therapy was
successfully applied in the case of nine patients (36%)
(P < 0.05). When the same treatments were applied to cases of
temporomandibular joint disease, 64% of drug-physical therapy-
occlusal splint and 36% of drug- physiotherapy-occlusal splint-
botox treatments were found to be successful.
The mean age of the nine patients (4 males and 5 females) who
underwent botox treatment was 33.67 years.
Bite force decreased in 4 patients, increased in 3 patients and
remained the same in 2 patients after treatment (P > 0.05). Pain
assessment was carried out according to VAS guidelines and the
reduction in pain was significant (P < 0.05). Mouth openness was
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reduced in two patients, increased in six patients, and there was no
change in the case of one patient (P > 0.05).
The effect of Botulinum toxin type A injection on bite force,
biting pain and mouth openness is shown in the following graphic
(Fig.1).
No signs were found of xerostomia jaw weakness, difficulty
chewing and cosmetic side effects at six months’ follow-up.
6. Discussion
Temporomandibular disorders describe a spectrum of disorders
causing pain in the temporomandibular joint and surrounding
structures due to hyperfunction of the muscles of mastication
[5]. The main aim of the treatment of temporomandibular joint
dysfunction is the remission of pain in the muscles and joints and
restoration of the physiological norm for proper muscle tension
and loading of the joint [2]. In treating TMJ dysfunction, the use of
analgesics, anti-inflammatories, muscle relaxants and antidepres-
sants is strongly recommended, especially when accompanied by
pain, inflammation and stress. Drug treatment alone was sufficient
in 10.5% of our patients. We take the view that pharmacological
treatment has a relaxing effect, especially for those patients with
psychological problems, those with an excessive habit of clenching
their teeth and those experiencing particular pain. This can
therefore be a valuable initial step in the treatment process.
Supportive treatment is limited in the treatment of muscular-
originated temporomandibular joint diseases. Physical therapy
and medication are reversible and offer only short-term symptom
relief. Symptoms may recur. BTX-A injection into the chewing
muscles is an effective method for the treatment of muscular
temporomandibular joint diseases [18,19].
Botulinum toxin type A, administered by injection into the
masticatory muscles, has been reported to be an effective
treatment method for TMJ dysfunction in recent years. In our
study, a total of 100 units of Botulinum toxin type A, within the
recommended safety limits, was administered. No side effects
were observed.
Although originally recommended for treating focal dystonias,
botulinum toxin has also been demonstrated to provide pain relief
for the head (migraine, tension headaches) and neck (cervical
Fig. 1. Botulinum toxin type A injection effect on pain (green), bite force (blue) and
mouth openness (yellow).
Please cite this article in press as: Sipahi Calis A, et al. The use of botulinum toxin-a in the treatment of muscular temporomandibular
joint disorders. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.02.015
3
dystonia, whiplash-associated neck pain), suggesting a potential
role in the treatment of TMDs. The diverse group of TMDs
relating to the orofacial musculature which have shown early
evidence of response to treatmentwith botulinum toxin includes
the following:
 bruxism and clenching;
 oromandibular dystonias;
 myofascial pain (often due to parafunction);
 myofascial pain with secondary TMJ involvement;
 trismus;
 hypermobility;
 masseter and temporalis hypertrophy;
 headaches [7].
In the case of temporomandibular joint disease, pain arising
from the articular section of the joint and from muscular structures
is usually evident. Inflammation and articular pain in the joint can
have a negative effect on degree of mouth openness, masticatory
strength, bite strength and pain felt when biting. The source of
chronic myofascial pain is not clear [18,20].
In a study conducted on patients with temporomandibular
joints, pain experienced by the patient decreased by 90% after BTX-
A application to the masticatory muscles [21]. Freund and
Schwartz found that in patients with temporomandibular joints,
the pain in these muscles was reduced by 50% with BTX-A. In our
study, pain was also found to be reduced after BTX application, but
this time by 100%.
Other studies by Freund and Schwartz found that patients with
temporomandibular joint dysfunction experienced reduced pain
and bite strength during the active BTX-A period following
injection. It was observed that the degree of mouth opening also
increased. Three processes have been recognized in relation to
BTX-A’s effectiveness. Firstly, muscle loosening: reduced muscle
tone is explained by the inhibition of alpha and gamma neurons.
Secondly, the mechanism associated with reduced inflammation in
the joint and muscle. Inflammation of the joint restricts the
movement of the capsules and ligaments. The third process is the
relief of pain and the increase in the degree of mouth opening.
These three processes act together to enhance efficiency and
mouth openness [18,22].
In their study, Schwartz et al. reported that BTX-A reduced pain
and bite strength after intramuscular injection into the area of the
muscular TMJ dysfunction and increased mouth opening [23]. Our
results indicated that, after BTX-A administration, bite strength
decreased in four out of nine patients, but this result was not
significant (P > 0.005) Pain assessment was carried out according
to VAS gudelines, and a total of nine patients showed a reduction in
pain. This result was statistically significant (P < 0.005). After
millimetric assessment of the degree of mouth opening, six out of
nine patients showed an increase after treatment. This change was
not statistically significant (P > 0.005) (Fig. 1).
This result can be attributed to the low number of patients
undergoing BTX-A. Evaluation of a large sample of patients would
make the results of the study more meaningful. However, the high
price of the drug, the side effects which may occur, and the fact that
it is a new treatment modality have all contributed to a limited
number of patients receiving BTX-A when other treatments have
failed. We believe that a study involving a large number of patients
is required which would help determine the potential for increased
use of this treatment in future.
We are of the opinion that it is useful to use this substance,
which is widely used in cosmetics, in the treatment of temporo-
mandibular joint diseases of muscular origin. Of the 25 patients
with muscular temporomandibular joint dysfunction, 16 (64%)
responded to the treatment with medication-physiotherapy-
occlusal splint. Nine patients (36%) who did not respond to
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medication-physiotherapy-occlusal splint were successful with
BTX-A administration (P < 0.005). This suggests that pharmaco-
logical treatment, physiotherapy and occlusal splint should be
applied first in the treatment of patients with myogenic origin of
temporomandibular joint dysfunction, but that BTX-A application
is a new, viable treatment option in cases where other treatments
have not proved successful.
Botulinum toxin has the advantage of being a minimally
invasive intervention and an effective treatment method in
patients who do not respond to more conservative treatments
(soft diet, non-steroid anti-inflammatories and oral appliance). In
addition, the relatively short application time required for
botulinum toxin, the low pain level associated with it during
application and the low risk of complication can all be listed as
significant advantages [4,10]. In accordance with the literature, we
think that the use of botulinum toxin in the treatment of muscular
temporomandibular joint disorder is a viable and effective
treatment method.
In our study group, 25 patients with TMJ dysfunction of
muscular origin were treated with Botulinum toxin type A
injection, including nine patients who did not benefit from
drug-physical therapy-occlusal splint. Our results indicate that
this new treatment is an effective method for the treatment of
muscular TMJ disorder.
7. Conclusion
For the treatment of muscular temporomandibular joint
diseases, it is important firstly that the patient should be examined
with care and then diagnosed correctly. The mechanics behind the
condition and its causes should be properly understood before
beginning the application of conservative treatments.
When choosing among the treatment modalities for temporo-
mandibular joint dysfunction, the most risk-free one should be
initiated first and the others should be started only if necessary.
Treatments which may lead to serious and irreversible outcomes
should be avoided. In other words, considered and patient-
centered treatments should always be preferred to those involving
surgical intervention.
In conclusion, the application of Botulinum toxin is a treatment
option which can be safely and effectively used for patients with
muscular temporomandibular joint disease when traditional,
established medical treatments have failed.
Disclosure of interest
The authors declare that they have no competing interest.
Please cite this article in press as: Sipahi Calis A, et al. The use of botulinum toxin-a in the treatment of muscular temporomandibular
joint disorders. J Stomatol Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.jormas.2019.02.015
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