1. Botulinum Toxin in Dentistry David Mock, DDS, PhD, FRCD(C) Professor, Oral Pathology/Oral Medicine, Faculty of Dentistry, University of Toronto Professor, Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto Wasser Pain Management Centre, Mount Sinai Hospital Departments of Dentistry and Pathology, Mount Sinai Hospital

2. Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C 1, C 2, D, E, F and G). All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. – Indian J Dermatol. 2010 Jan-Mar; 55(1): 8–14.

3. Mechanism of Action of Botulinum Toxin (Arnon et al., 2001)

4. B. Subin, S. Saleemi, G..A. Morgan, F. Zavisca, R..C. Cork: Treatment of Chronic Low Back Pain by Local Injection of Botulinum Toxin-A. The Internet Journal of Pain, Symptom Control and Palliative Care. 2003 Volume 2 Number 2. DOI: 10.5580/4ed

5. Proprietary NameNon-Proprietary Name Botox / Botox CosmeticOnabotulinumtoxinA Xeomin / Xeomin CosmeticIncobotulinumtoxinA DysportAbobotulinumtoxinA MyoblocRimabotulinumtoxinB Botox is indicated for the treatment of severe muscle spasm in the neck, eye and foot, for chronic migraines, incontinence, and for excessive sweating. Botox Cosmetic is indicated for cosmetic purposes, to treat facial wrinkling. Dysport is indicated for the temporary improvement in the appearance of moderate to severe wrinkles in adult patients less than 65 years of age. Xeomin is indicated for severe muscle spasm in the neck, eye and arm. Xeomin Cosmetic is indicated for the temporary improvement of moderate to severe frown lines in adult patients. Myobloc is indicated for the treatment of adult patients with severe muscle spasm in the neck. Health Canada, January 21, 2013

6. Therefore: There is no Health Canada accepted indication for the use of botulinum toxin within the scope of practice of dentistry in Ontario as defined by the RCDSO All other therapeutic applications of botulinum toxin are “off label” uses and the patient must be so informed The regulatory bodies in British Columbia and Alberta have accepted the use of botulinum toxin for cosmetics as within the scope of practice of dentistry

7. Contraindications Muscular disorders such as myasthenia gravis, Eaton Lambert Syndrome, ALS Allergy or sensitivity to botulinum toxin Infection at injection site Patient is scheduled to have a GA for surgery Pregnancy or impending pregnancy The effect can be increased by aminoglycoside antibiotics (e.g. streptomycin, tobramycin, neomycin, gentamicin, netimaicin, kanamycin, amikacin,), spectinomycin, polymyxins, tetracycline, lincomycin

8. Adverse Reactions to Botulinum Toxin A Local weakness represents the expected pharmacological action of botulinum toxin. Tenderness, bruising, localized pain may be expected, as with any type of intramuscular injection. Rarely: skin rash, pruritis, allergic reaction, facial paralysis, malaise, general weakness,, nausea, headache, drowsiness, stiffness, dry mouth, rhinitis, and hypertonia Numbness, diplopia, ptosis, dyspnea, fever, cardiac problems (including arrhythmia and myocardial infarction, some with fatal outcomes), rare spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility.

9. Summary of reports of adverse reactions suggestive of distant toxin spread suspected of being associated with botulinum toxin type A submitted to Health Canada as of Mar. 28, 2008**

10. Off Label Uses in Dentistry Intraoral to relieve occlusal forces on newly placed dental implants or restorations (* suggested but not proven) Intra-oral or extra-oral to reduce high lip lines or perioral age related changes (aesthetic) Intra-oral or extra-oral for neuropathic pain – If unresponsive to accepted modalities Intra-oral and extra-oral for muscle spasm, parafunction or myofascial pain – If unresponsive to accepted modalities management of sialorrhea (*injection into the salivary glands, usually with imaging guidance)

11. RCDSO Policy Members who use botulinum toxin and dermal fillers should only do so for procedures that are within the scope of practice of dentistry. Members may inject botulinum toxin and/or dermal fillers – intraorally for either therapeutic or cosmetic purposes – extra-orally for therapeutic purposes, but in either case only if the member is appropriately trained and competent to perform the procedure(s). It is not within the scope of practice and members are not authorized in Ontario to inject botulinum toxin or dermal fillers extra-orally for cosmetic purposes.

12. NOTE: Example applicable only to BOTOX, each agent should be considered according to manufacturers recommendation Quantity of Diluent Added * 50U Vial100U Vial200U Vial 1.0 ml5.0U10.0U20.0U 2.0 ml2.5U5.0U10.0U 4.0 ml1.25U2.5U5.0U 8.0 ml-------------1.23U2.5U * 0.9% sodium Chloride (Injectable)`

13. TEMPOROMANDIBULAR DISORDERS

14. Treatment of Temporomandibular Disorders with Botulinum Toxin. Schwartz, Marvin; Freund, Brian Clinical Journal of Pain. 18(6) Supplement:S198-S203, November/December 2002. A good general rule is 5U per injection site with maximums/muscle as noted above.

15. Masseter Muscle and Temporalis Muscle

16. (Difficult)

18. NEUROPATHIC PAIN

19. What is Neuropathic pain? IASP (original): pain initiated or caused by a primary lesion or dysfunction in the nervous system “Pain arising as direct consequence of a lesion or disease affecting the somatosensory system”Expert panel Possible Mechanisms Inhibit peripheral sensitization of nociceptive fibres thereby reducing central sensitization thru inhibiting release of glutamate and substance P (Aoki 2003) Inhibits depolarization-induced release of substance P and CGRP from terminals (Cutrer et al 2010) Trigeminal Nerve Pain Conditions Trigeminal Neuralgia Secondary Trigeminal Neuralgia or Central Neuropathic Pain including MS Trigeminal Neuropathic Pain Atypical Facial Pain Post-herpetic Neuralgia Never the first line of treatment but when all conventional treatments have failed and the patient’s condition warrants: When considered – intradermal, intramucosal, submucosal, subcutaneous injection

20. OTHER POSSIBLE APPLICATIONS

22. COSMETIC APPLICATION OF BOTULINUM TOXIN Note: Not defined as within the scope of practice of dentistry in the Province of Ontario and a number of other Canadian provinces

24. *From Allergan for Botox ©