Orofacial Applications of Botulinum Neurotoxin

The following is the first article in a series to address applications of Botulinum neurotoxin. The following article is presenting a short review of the Orofacial applications of BoNT, with a focus on the benefit of using the Myoguide™ EMG/ESTIM BoNT injection guidance system. The information within, is simply informative and not considered to be instructive, in any way. Please have a look at the details within the appropriate reference materials for more details.

Botulinum toxin (BoNT) is a neurotoxin produced by the bacterium Clostridium Botulinum. There are seven types of BoNT (A–G) which bind and cleave one of several neuronal cellular proteins including SNAP-25, Syntaxin or VAMP/Synaptobrevin. 

The outcome of BoNT application results in the inhibition of release of acetylcholine (Ach) from the motor neuron terminals resulting in muscle weakness or paralysis.  Duration of action depends on cellular regeneration mechanisms, which can take 3-6 months.

The orofacial complex consists of the muscles of:

  • The jaw
  • Lips
  • Tongue
  • Soft palate
  • Larynx

BoNT has several orofacial applications and is effective in reducing pain and/or muscle activity in chronic migraine, myofascial pain, orofacial movement disorders, neuropathic pain, trigeminal neuralgia and bruxism.  Other applications include control of excess salivation (sialorrhea) and gustatory sweating (Frey Syndrome), and spasmodic dysphonia (1-9,27-28).

BoNT was originally thought to reduce orofacial pain through inhibition of muscle activity, however, current evidence suggests that there may be analgesic properties as a result of its ability to inhibit the release of substance P, calcitonin gene-related peptide and transient receptor potential, vanilloid receptor type 1 (31).

The net result may translate into reduced pain and neurogenic inflammation in the peripheral and central nervous system. This may be synergistic with the ability of BoNT to block neuromuscular transmission (29).

Injection techniques are usually fairly straight forward and can be performed with or without electromyography (EMG) guidance, depending on the indication.  

We recommend using the Myoguide Injection guidance system, regarding superior design and access to many useful built-in features, to support both EMG and STIM guidance procedures. Visit the Myoguide Store! to get started.

Orofacial movement disorders

Orofacial movement disorders include orofacial dystonia and orofacial dyskinesia (32).

These conditions can affect multiple orofacial muscles including platysma, orbicularis oris, buccinator, genioglossus, geniohyoid, digastric and intrinsic tongue muscles. The net result can be involuntary jaw opening, clenching, tongue thrusting and facial tics. They have the potential to result in Temporomandibular (TM) dysfunction when the masseter, temporalis, medial pterygoid muscles are involved. It may also result in TM joint dislocation when the lateral pterygoid muscle is involved.

BoNT remains an effective treatment particularly for focal dystonia and dyskinesia.

There are two basic options for accessing these muscles, including either intraoral or extraoral approaches.  Both require EMG guidance (11-15).  

Temporalis and Masseter muscles injections are fairly straight forward, whereas injection for the Medial Pterygoid muscle is more challenging, and more subject to iatrogenic effects.

The techniques for accessing the Lateral Pterygoid muscle is less challenging, however, the extraoral approach does have risks (33).

Neuropathic pain

BoNT is known to inhibit neuromodulator and transmitter secretion that may reduce central neuropathic pain.

The proposed mechanism of action includes a reduction in the release of excitatory glutamate, SP, and CGRP. Furthermore, BoNT reduces the expression of TRPV1 that is associated with capsaicin-evoked and calcium channel responses (16,17).

The injection technique in the management of neuropathic pain is unique in that the BoNT is injected subcutaneously in the dermatome overlying the neuropathic pain. This procedure does not require EMG guidance.

Trigeminal Neuralgia

Trigeminal Neuralgia (TN) is not synonymous with neuropathic pain. The etiology of TN remains unclear, although compression of the trigeminal nerve root by the superior cerebellar artery is thought to result in focal demyelination and paroxysms of pain. Additional causes include tumors, multiple sclerosis and post-viral syndromes.

The mainstay of treatment is medication including carbamazepine, oxycarbamazepine, phenytoin, gabapentin, pregabalin and baclofen. Surgical treatment involves Gasserian ganglion rhizotomy, gamma knife and microvascular decompression (18-20).

The mechanism of action of the BoNT is thought to be similar to that of neuropathic pain. The injection technique is also identical. The time to maximal pain reduction for both neuropathic pain and TN appears to be 4–8 weeks. This is much longer than the 1–2 weeks for muscular injection and may reflect the need for retrograde axonal transport to the CNS (18-20).

Bruxism

The beneficial effect of BoNT on sleep-related bruxism has been reported (21,22). It appears to reduce the intensity of muscle activity within the masseter and temporalis muscles with a reduction in self-reported pain and jaw stiffness. The injection technique and dosing is identical to that for myofascial pain.

Frey syndrome

Frey syndrome is a rare complication following parotid and temporomandibular joint surgery. It results in gustatory sweating during eating. The parotid gland receives parasympathetic secretory innervation via a complicated neural pathway that involves the auriculotemporal nerve and the release of Ach.

The sweat glands of the skin are innervated by the sympathetic fibers originating from superior cervical ganglion traveling via the same auriculotemporal nerve. Parotid and temporomandibular joint surgery are thought to cause an injury to the auriculotemporal nerve leading to inappropriate parasympathetic innervation of the overlying sweat glands.

This can result in profuse sweating during mastication. The diagnosis of Frey syndrome can be made using the minor iodine/starch test. This test will also delineate exact area of skin that is affected. This should be outlined with a skin marker. BoNT can be injected subcutaneously. The therapeutic effect is generally apparent within a week and should last 3–6 months (23).

Sialorrhea

The excessive production of saliva or the inability to adequately swallow saliva may result in drooling. This is often seen in patients with neurological disorders including those with developmental delay, cerebral palsy, amyotrophic lateral sclerosis, Parkinson’s disease, cerebrovascular accident and traumatic brain injury.

Antisialagogues have limited efficacy and result in systemic side effects. Surgical procedures including salivary gland duct ligation and sialodochoplasty to reposition ducts has also been described. The use of BoNT to reduce salivation has grown in popularity with promising results (24-26).

The technique for parotid and submandibular gland injection is relatively simple. The use of ultrasound to identify the precise location of the gland and appropriate intraglandular injection is encouraged. The ideal dose varies depending on the gland size and the severity of hypersalivation and drooling.

Spasmodic Dysphonia

The disorder is due to the situation where the (laryngeal) muscles that generate a person’s voice go into periods of spasm. This results in breaks or interruptions in the voice, often every few sentences, which can make a person difficult to understand (27,28).  See our animated video illustrating the approach for vocal cord injections using Myoguide.

Myoguide™ EMG/ESTIM BoNT injection guidance system is designed to amplify EMG signals from muscle and provide audio and visual feedback to assist clinicians in locating areas of muscle activity.

Myoguide also has an integrated and well featured stimulator, capable of stimulation in either 1.0 mA or 0.1 mA steps, for muscle, nerve, and motor endplate location procedures.

Myoguide supports injection of neuromodulators and both chemodenervation and neurolytic procedures, as well as, peripheral nerve stimulation. Learn more about how to use Myoguide

References

  1. Gazerani P, Au S, Dong X, et al. Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis. Pain 2010;151:606-16.
  2. Kleen JK, Levin M. Injection therapy for headache and facial pain. Oral Maxillofac Surg Clin North Am 2016;28:423-34.
  3. Frampton JE. OnabotulinumtoxinA (BOTOX®): a review of its use in the prophylaxis of headaches in adults with chronic migraine. Drugs 2012;72:825-45.
  4. Luvisetto S, Gazerani P, Cianchetti C, et al. Botulinum toxin type a as a therapeutic agent against headache andrelated disorders. Toxins (Basel) 2015;7:3818-44.
  5. Schiffman E, Ohrbach R. Executive summary of the Diagnostic Criteria for Temporomandibular Disorders for clinical and research applications. J Am Dent Assoc 2016;147:438-45.
  6. Fallah HM, Currimbhoy S. Use of botulinum toxin A for treatment of myofascial pain and dysfunction. J OralMaxillofac Surg 2012;70:1243-5.
  7. Sunil Dutt C, Ramnani P, Thakur D, et al. Botulinum toxin in the treatment of muscle specific Oro-facial pain: a literature review. J Maxillofac Oral Surg 2015;14:171-5.
  8. Baker JS, Nolan PJ. Effectiveness of botulinum toxin type A for the treatment of chronic masticatory myofascial pain:a case series. J Am Dent Assoc 2017;148:33-9.
  9. Sidebottom AJ, Patel AA, Amin J. Botulinum injection for the management of myofascial pain in the masticatorymuscles. A prospective outcome study. Br J Oral Maxillofac Surg 2013;51:199-205.
  10. Connelly ST, Myung J, Gupta R, et al. Clinical outcomes of Botox injections for chronic temporomandibular disorders: do we understand how Botox works on muscle, pain, and the brain? Int J Oral Maxillofac Surg 2017;46:322-7. Bakke
  11. M, Baram S, Dalager T, et al. Oromandibular dystonia, mental distress and oro-facial dysfunction-A follow-up 8-10 years after start of treatment with botulinum toxin. J Oral Rehabil 2019;46:441-9.
  12. Clark GT, Ram S. Orofacial movement disorders. Oral Maxillofac Surg Clin North Am 2016;28:397-407.
  13. Mendes RA, Upton LG. Management of dystonia of the lateral pterygoid muscle with botulinum toxin A. Br J Oral Maxillofac Surg 2009;47:481-3.1
  14. Renapurkar SK, Laskin DM. Injectable agents versus surgery for recurrent temporomandibular joint dislocation. Oral Maxillofac Surg Clin North Am 2018;30:343-9.
  15. Yoshida K. Botulinum neurotoxin injection for the treatment of recurrent temporomandibular joint dislocation with and without neurogenic muscular hyperactivity. Toxins (Basel) 2018;10:174.
  16. Park J, Chung ME. Botulinum toxin for central neuropathic pain. Toxins (Basel) 2018;10:224.
  17. Moreau N, Dieb W, Descroix V, et al. Topical review: potential use of botulinum toxin in the management of painful posttraumatic trigeminal neuropathy. J Oral Facial Pain Headache 2017;31:7-18.
  18. Burmeister J, Holle D, Bock E, et al. Botulinum neurotoxin type A in the treatment of classical Trigeminal Neuralgia (BoTN): study protocol for a randomized controlled trial. Trials 2015;16:550.
  19. Castillo-Álvarez F, Hernando de la Bárcena I, Marzo-Sola ME. Botulinum toxin in trigeminal neuralgia. Med Clin (Barc) 2017;148:28-32.
  20. Li S, Lian YJ, Chen Y, et al. Therapeutic effect of Botulinum toxin-A in 88 patients with trigeminal neuralgia with 14-month follow-up. J Headache Pain 2014;15:43.
  21. De la Torre Canales G, Camara-Souza MB, do Amaral CF, et al. Is there enough evidence to use botulinum toxin injections for bruxism management? A systematic literature review. Clin Oral Investig 2017;21:727-34.
  22. Shim YJ, Lee MK, Kato T, et al. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxismpatients: a polysomnographic evaluation. J Clin Sleep Med 2014;10:291-8.
  23. Jansen S, Jerowski M, Ludwig L, et al. Botulinum toxin therapy in Frey’s syndrome: a retrospective study of 440 treatments in 100 patients. Clin Otolaryngol 2017;42:295-300.
  24. Alvarenga A, Campos M, Dias M, et al. BOTOX-A injection of salivary glands for drooling. J Pediatr Surg 2017;52:1283-6.
  25. Sridharan K, Sivaramakrishnan G. Pharmacological interventions for treating sialorrhea associated with neurological disorders: a mixed treatment network meta-analysis of randomized controlled trials. J Clin Neurosci 2018;51:12-7.
  26. Weitzman RE, Kawai K, Nuss R, et al. A 10-year retrospective review of botulinum toxin injections and surgical management of sialorrhea. Cureus 2020;12:e7916.
  27. Cannito, M. P., Kahane, J. C., & Chorna, L. (2008). Vocal aging and adductor spasmodic dysphonia: response to botulinum toxin injection. Clinical interventions in aging3(1), 131–151. https://doi.org/10.2147/cia.s1416
  28. Simpson, C Blake, et al. “Botulinum Toxin Treatment of False Vocal Folds in Adductor Spasmodic Dysphonia: Functional Outcomes.” The Laryngoscope, vol. 126, no. 1, 2016, pp. 118-21.
  29. Bouloux GF. Botulinum toxin (Botox). Front Oral Maxillofac Med 2022;4:4 Front Oral Maxillofac Med 2022;4:4 | http://dx.doi.org/10.21037/fomm-20-42
  30. Gatto, K. K. (2015). Understanding the orofacial complex: Muscle Manual. Outskirts Press.
  31. Matak I, Bölcskei K, Bach-Rojecky L, Helyes Z. Mechanisms of Botulinum Toxin Type A Action on Pain. Toxins (Basel). 2019 Aug 5;11(8):459. doi: 10.3390/toxins11080459. PMID: 31387301; PMCID: PMC6723487.
  32. Skármeta, N. P. , Espinoza-Mellado, P., & Pedro Chana, P. (2018). Orofacial Dystonia and Other Oromandibular Movement Disorders. In (Ed.), Dystonia – Different Prospects. IntechOpen. https://doi.org/10.5772/intechopen.78607
  33. Taema, M., Nabi, N.A., Ibrahim, S. et al. Assessment of anterior positioning splint in conjunction with lateral pterygoid BTX injection to treat TMJ disc displacement with reduction — a preliminary report. Maxillofac Plast Reconstr Surg 43, 33 (2021). https://doi.org/10.1186/s40902-021-00317-3