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Botulinum Toxin for Orofacial Pain Management: Fiction or Fact?

By Steven D. Bender, D.D.S.

Botulinum toxin is a family of neurotoxic proteins produced by the bacterium clostridium botulinum. The toxin works primarily by inhibiting the release of acetylcholine, a neurotransmitter that plays a crucial role in muscle contraction, from nerve terminals. By blocking the release of acetylcholine, botulinum toxin prevents muscle contraction, leading to muscle paralysis. There are seven known serotypes of botulinum toxin, labeled from A to G, with serotypes A and B being the most used in medical and cosmetic applications. Botulinum toxin is used therapeutically to treat a variety of conditions such as muscle spasms, dystonia, excessive sweating, chronic migraines, and overactive bladder. In the field of cosmetics, it is utilized to reduce the appearance of facial wrinkles and fine lines by temporarily paralyzing the underlying muscles of facial expression. The different serotypes of botulinum toxin allow for targeted treatment options based on the specific needs and indications of patients, and their usage requires expertise and careful administration to ensure optimal results and minimize potential side effects.

Botulinum toxin has also been found to have an impact on pain mediating neurotransmitters, contributing to its therapeutic effects in pain management.1 Research suggests that botulinum toxin inhibits the release of various neurotransmitters involved in pain signaling, including substance P, glutamate, and calcitonin gene-related peptide (CGRP). Substance P is a neuropeptide associated with transmitting pain signals, while glutamate acts as an excitatory neurotransmitter involved in pain processing. CGRP, a potent vasodilator, is widely distributed in nociceptive pathways in the human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP has been shown to play a significant role in migraine pathophysiology.2 By blocking the release of these neurotransmitters, botulinum toxin can help reduce pain perception and alleviate symptoms associated with conditions such as chronic migraines, neuropathic pain, and muscle spasticity. In fact, studies have demonstrated the effectiveness of botulinum toxin injections in reducing pain intensity and frequency in these conditions.3 4 These findings highlight the multifaceted mechanisms of botulinum toxin and its ability to modulate pain pathways, providing a promising approach to pain management. However, it is important to note that the clinical effects of botulinum toxin are relatively short lasting. The onset of action tends to be approximately 1-14 days and peaks at around 4 weeks. The effects will then wear off after approximately 10-12 weeks. As a therapy, it should be considered temporary and palliative.

The therapeutic application of botulinum toxin in the field of dentistry has gained significant attention over the past decade, particularly in treating orofacial pains (OFPs) disorders. OFP disorders are typically complex and multifactorial conditions that affects the head, face, and mouth, causing discomfort and in some cases, disability for patients. This essay will briefly explore the use of botulinum toxin in the management of some of the more common OFP presentations.

The use of botulinum toxin in the management of OFP disorders has shown promising results in several clinical trials. One of the most common OFP conditions treated with botulinum toxin is temporomandibular disorders (TMDs), which is a group of conditions that affect the temporomandibular joint (TMJ), the masticatory muscles, and the associated structures. A randomized controlled trial conducted by Guarda-Nardini et al. demonstrated that botulinum toxin injections into the masseter muscles of patients with TMD significantly reduced pain intensity and improved jaw function as compared to placebo.5 However, a recent systematic review found that while there is good evidence to support the use of botulinum toxin injections for treatment of masseter muscle hypertrophy and equivocal evidence for myogenous TMDs, there is little evidence for the use in TMJ specific disorders.6 It’s important to note that botulinum toxin injections into the masticatory muscles may reduce the intensity of bruxism activity but will not affect the number of events.7 It is also important to mention that in some instances, the use of botulinum toxin injections in the masticatory muscles may lead to negative outcomes such as osteopenic changes and fracture.8-11

Another OFP disorder that has been treated with botulinum toxin with some supportive data is trigeminal neuralgia (TN). TN is a condition characterized by brief but severe facial pain that affects one or more branches of the trigeminal nerve. In one randomized placebo controlled trial, it was found that botulinum toxin A may be an effective and safe therapy for TN treatment.12 Several systematic reviews have also found promising results for TN as well as other oral and facial neuropathic pain disorders.13-15

Burning Mouth Syndrome (BMS) is sometimes considered to be a neuropathic pain disorder and is characterized by a burning sensation in the oral cavity without any identifiable cause. A case report involving 4 patients with BMS where the botulinum toxin was injected into the anterolateral areas of the tongue as well as the lower lip showed promising results lasting up to 12 weeks.16

Botulinum toxin injections are generally safe and well-tolerated by patients when administered by a trained professional. However, like any medical procedure, there are potential risks and side effects associated with the use of botulinum toxin. The most common side effects include pain, bruising, swelling, and redness at the injection site. These side effects are usually mild and resolve within a few days. Less common side effects include muscle weakness, drooping of the eyelids or other facial areas, double vision, and difficulty swallowing, which can occur if the toxin spreads beyond the intended injection site. However, these side effects are usually temporary and resolve within a few weeks.

In conclusion, the use of botulinum toxin for OFP disorders may prove to be a valuable alternative treatment option. Its ability to work both peripherally and centrally can potentially provide effective relief for conditions such as myogenous TMDs and other OFPs. The toxin’s relatively minimal side effects make it a promising alternative to some of the more traditional pharmacologic therapies. However, further research is needed to optimize dosing and injection location protocols and expand our understanding of its mechanisms of action. As we continue to explore and refine the use of botulinum toxin, it certainly may hold potential for improving the quality of life for individuals suffering from OFP disorders, offering them renewed comfort and functionality.

  1. Park HJ, Lee Y, Lee J, Park C, Moon DE. The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can J Anaesth 2006;53(5):470-7.
  2. Durham PL. Calcitonin gene-related peptide (CGRP) and migraine. Headache 2006;46 Suppl 1(Suppl 1):S3-8.
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  7. Shim YJ, Lee MK, Kato T, et al. Effects of botulinum toxin on jaw motor events during sleep in sleep bruxism patients: a polysomnographic evaluation. J Clin Sleep Med 2014;10(3):291-8.
  8. Chang CS, Bergeron L, Yu CC, Chen PK, Chen YR. Mandible changes evaluated by computed tomography following Botulinum Toxin A injections in square-faced patients. Aesthetic Plast Surg 2011;35(4):452-5.
  9. Raphael KG, Tadinada A, Bradshaw JM, et al. Osteopenic consequences of botulinum toxin injections in the masticatory muscles: a pilot study. J Oral Rehabil 2014;41(8):555-63.
  10. Hong SW, Kang JH. Decreased mandibular cortical bone quality after botulinum toxin injections in masticatory muscles in female adults. Sci Rep 2020;10(1):3623.
  11. Kahn A, Kun-Darbois JD, Bertin H, Corre P, Chappard D. Mandibular bone effects of botulinum toxin injections in masticatory muscles in adult. Oral Surg Oral Med Oral Pathol Oral Radiol 2020;129(2):100-08.
  12. Wu CJ, Lian YJ, Zheng YK, et al. Botulinum toxin type A for the treatment of trigeminal neuralgia: results from a randomized, double-blind, placebo-controlled trial. Cephalalgia 2012;32(6):443-50.
  13. Hu Y, Guan X, Fan L, et al. Therapeutic efficacy and safety of botulinum toxin type A in trigeminal neuralgia: a systematic review. J Headache Pain 2013;14(1):72.
  14. Wei J, Zhu X, Yang G, et al. The efficacy and safety of botulinum toxin type A in treatment of trigeminal neuralgia and peripheral neuropathic pain: A meta-analysis of randomized controlled trials. Brain Behav 2019;9(10):e01409.
  15. Morra ME, Elgebaly A, Elmaraezy A, et al. Therapeutic efficacy and safety of Botulinum Toxin A Therapy in Trigeminal Neuralgia: a systematic review and meta-analysis of randomized controlled trials. J Headache Pain 2016;17(1):63.
  16. Restivo DA, Lauria G, Marchese-Ragona R, Vigneri R. Botulinum Toxin for Burning Mouth Syndrome. Ann Intern Med 2017;166(10):762-63.

Dr. Steven D. Bender, Diplomat American Board of Orofacial Pain, is Clinical Associate Professor, Texas A&M University School of Dentistry, Dallas.