Temporomandibular disorder is a common cause of chronic facial pain and is known to interfere with personal relations, professional duties, and overall quality of life. Appropriate diagnosis allows physicians to identify the disorder and initiate an effective therapeutic plan. Botulinum toxin can provide long-term relief of TMD by reducing the intensity, frequency, and duration of recurrent episodes. Adverse effects from BoNT injections are uncommon, mild and transient making it an attractive option for adjunctive therapy for myofascial TMD in patients who have failed initial conservative therapy and systemic pharmacotherapy.
The temporomandibular joint (TMJ) is a hinged synovial joint that connects the mandible to the temporal bone at the skull base, and the posterior border of the TMJ is the anterior border of the external auditory canal. The TMJ is one of the few synovial joints with an articular disc and it functions as both a hinge joint and a sliding joint. It is therefore classified as a ginglymoarthrodial joint. Adduction of the mandible, or mouth closing, is performed by the actions of the masseter, temporalis, and medial pterygoid muscles. Abduction, or mouth opening, is performed by the lateral pterygoids and digastric musculature. The lateral deviation occurs by the action of the contralateral lateral pterygoid muscles, and protrusion of the mandible occurs when right and left lateral pterygoid muscles contract simultaneously.
The diagnosis of TMJ dysfunction is based on history and physical exam findings. Patients should be asked about nighttime bruxism, jaw soreness, morning headaches, use of mouth orthodonitics, or history of trauma. Questions regarding the patient’s personal habits and diet should be evaluated to reduce behaviors that may place additional stress on the TMJ, like frequent gum chewing. Symptoms of depression, anxiety or recent stressors should also be assessed as these conditions often lead to unconsciously clench.
Signs and symptoms of TMD may include joint or muscular pain with or without jaw opening/closing, limited jaw movement, cracking or popping sounds at the TMJ with movement, or headaches. Patients often present with otalgia, ear fullness or tinnitus which is referred from the anterior external auditory canal and is a shared border with the posterior TMJ. In addition, otalgia may be referred from muscles of mastication as some middle ear muscles (tensor tympani and tensor palatini) are also innervated by the trigeminal nerve. Some patients with TMD have complained of unilateral and boring orbital or periorbital pain, which could be neurogenic or due to hyperfunctioning temporalis muscles often present with otalgia, ear fullness or tinnitus which is referred from the anterior external auditory canal, and is a shared border with the posterior TMJ.
The first indication that BoNT could be useful for treating pain was observed from anecdotal reports of patients treated for hyperfunctional facial lines who reported reduced frequency and severity of headache. Soon thereafter, the pain-relieving effect of BoNT was reported during the treatment of oromandibular dystonia and cervical dystonia. Today, BoNT is used for pain relief in numerous conditions including tension headaches, migraine headaches, post-herpetic neuralgia and myofacial TMD.
BoNT is a 150-Kilodalton exotoxin produced from clostridium botulinum, whose action is mediated through the cleavage of docking proteins that are responsible for membrane fusion of pre-synaptic vesicles. Type A bolulinum toxin (BoNT-A) cleaves the membrane associated protein “synaptosomal-associated protein 25” (SNAP-25) which is a member of the “soluble N-ethylmaleimide sensitive factor attachment protein receptor protein (SNARE). Type B botulinum toxin (BoNT-B) cleaves synaptobravin, which is part of the vesicular-associated membrane protein (VAMP). Cleavage of these docking proteins leads to muscle weakens by inhibition of acetylcholine (Ach) release at the neuromuscular junction.
The most commonly affected muscles are the temporalis muscle, masseter muscle and lateral pterigoid muscles. The temporalis muscle and masseter muscle are almost always involved and usually manifest as direct muscle pain. Lateral pterygoids involvement usually manifests as buccal pain, lateral jaw deviation or bruxism.
The injections are performed under real-time ultrasound guidance. We typically use a concentration of 2.5–5.0 units per 0.1 mL of Botox with a starting dose of 10–25 units for each temporalis muscle, 25–50 units to the masseter muscles and 7.5–10 units to the lateral pterygoids. Subsequent doses are individualized and are based on the patients’ response. Botox diffuses to about 1 cm at each injection site, and affected areas may be left untreated if an inadequate number of sites are infiltrated within a single muscle group. To avoid an incomplete response, we advocate using lower concentrations at multiple sites with larger injection volumes.
Approximately 3-4 weeks after the initial injection, patients are reevaluated for any adverse effects and/or suboptimal responses. Some patients may require a booster injection at that time. Additional BoNT injections are directed by the patients’ history and clinical examination, and pain diaries are a useful guide to help in patient directed therapy. It may take several weeks before patients experience the maximum pain relief from BoNT. Although the typical duration of efficacy is 12 weeks, we have noted tremendous variability among patients with respect to optimal dosing frequency. Some patients experience relief well beyond the predicted pharmacokinetic duration of the drug supporting the possibility that BoNT does not strictly act at the periphery and may be involved in neuromodulation at the level of the central nervous system. It is important to note that an individual patient’s response to toxin may change over time, which further supports the importance of patient-directed dosing.
BoNT injection for TMD is administered in relatively small doses and way below the estimated lethal dose of approximately 3000 units. Because of the relative low dosing profile, adverse effects are uncommon and often mild. Difficulty chewing is the most common adverse effect, which results from local muscle weakness and is usually dose dependent. Muscle atrophy may result in cosmetic alterations and is another risk of the procedure. Higher volume of BoNT increased the risk of diffusion of toxin to nearby areas which may cause brow ptosis, blepharoptosis or diplopia if the temporalis muscle is injected too close to the orbit. Facial asymmetry may result if the masseter muscle is injected too close to the zygomaticus major. Dry mouth may occur if BoNT is injected into the parotid gland. Flu-like syndromes rarely occur and are usually of brief duration. In addition, with any injection there is an inherent risk associated with a needle puncture, such as bruising, local tenderness, infection and nerve injury.
Contraindications to BoNT use include a known allergy to BoNT, active inflammation or infection at the proposed injection site, pregnancy, breast-feeding, or chronic degenerative neuromuscular disorders like amyotrophic lateral sclerosis, myasthenia gravis, Lambert-Eaton syndrome, muscular dystrophy or multiple sclerosis. Patients taking aminoglycoside antibiotics should not receive BoNT injections because this class of antibiotics may interfere with the neuromuscular transmission of toxin and potentiate the effect of BoNT.
Numerous studies have shown that BoNT provides long-term relief of myofascial TMD by decreasing the intensity, frequency, and duration of recurrent episodes. Freund et al reported on 46 patients with TMD treated with 150 units of BoNT-A to the masseters and temporalis muscles. They found significant reductions in their subjective and objective pain scores, and all patients with restricted mouth opening had some degree of improved range of motion. They also reported successful treatment various conditions that fall under the general category of TMD such as bruxism and clenching, oromandibular dystonias, trismus, masseter and temporalis hypertrophy, and headaches.
In a multicenter randomized double-blind, placebo-controlled fixed-dose study (50 units Botox to each masseter muscle and 25 units Botox to each temporalis muscle), reduction of subjective pain and tenderness to palpation was greatest at eight weeks following injections. The authors of this study also noted a decrease in the average daily use of pain medication over the 16-week duration of this study.