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Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States

  • Other Pain (N Vadivelu and A Kaye, Section Editors)
  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Erbguth FJ, Naumann M. Historical aspects of botulinum toxin: Justinus Kerner (1786-1862) and the ‘sausage poison’. Neurology. 1999;53(8):1850–3.

    Article  CAS  PubMed  Google Scholar 

  2. Snipe PT, Sommer H. Studies on botulinus toxin: 3. Acid precipitation of botulinus toxin. J Infect Dis. 1928;43(2):152–60.

    Article  Google Scholar 

  3. Lamanna C, McElroy OE, Eklund HW. The purification and crystallization of clostridium botulinum type A toxin. Science. 1946;103(2681):613–4.

    Article  CAS  Google Scholar 

  4. Burgen ASV, Dickens F, Zatman LJ. The action of botulinum toxin on the neuro-muscular junction. J Physiol. 1949;109(1–2):10–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Jankovic J, Brin MF. Botulinum toxin: historical perspective and potential new indications. Muscle Nerve Suppl. 1997;6:S129–45.

    Article  CAS  PubMed  Google Scholar 

  6. Dowson AJ, Kilminster SG, Salt R. Clinical profile of botulinum toxin A in patients with chronic headaches and cervical dystonia: a prospective, open-label, longitudinal study conducted in a naturalistic clinical practice setting. Drugs R & D. 2008;9(3):147–58.

    Article  CAS  Google Scholar 

  7. Lew MF. Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. Clin J Pain. 2002;18(6 Suppl):S142–6.

    Article  PubMed  Google Scholar 

  8. Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Rivera Día RC, Lotero MAA, Suarez MVA, Saldarriaga SE, Martínez MG. Botulinum toxin for the treatment of chronic pain. Review of the evidence. Colomb J Anesthesiol. 2014;42(3):205–13.

    Article  Google Scholar 

  10. Sim WS. Application of botulinum toxin in pain management. Korean J Pain. 2011;24(1):1–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Persaud R, Garas G, Silva S, Stamatoglou C, Chatrath P, Patel K. An evidence-based review of botulinum toxin (Botox) applications in non-cosmetic head and neck conditions. JRSM Short Rep. 2013;4(2):10.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Yin S, Stucker FJ, Nathan CA. Clinical application of botulinum toxin in otolaryngology, head and neck practice (brief review). J La State Med Soc. 2001;153(2):92–7.

    CAS  PubMed  Google Scholar 

  13. Schmitt WJ, Slowey E, Fravi N, Weber S, Burgunder JM. Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial. Headache. 2001;41(7):658–64.

  14. Oliver M, MacDonald J, Rajwani M. The use of botulinum neurotoxin type A (Botox) for headaches: a case review. J Can Chiropr Assoc. 2006;50(4):263–70.

    PubMed Central  PubMed  Google Scholar 

  15. Cetinkaya A, Brannan PA. What is new in the era of focal dystonia treatment? Botulinum injections and more. Curr Opin Ophthalmol. 2007;18(5):424–9.

    Article  PubMed  Google Scholar 

  16. Ahsan SF, Meleca RJ, Dworkin JP. Botulinum toxin injection of the cricopharyngeus muscle for the treatment of dysphagia. Otolaryngol Head Neck Surg. 2000;122(5):691–5.

    CAS  PubMed  Google Scholar 

  17. Lakraj AA, Moghimi N, Jabbari B. Sialorrhea: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins. Toxins (Basel). 2013;5(5):1010–31.

    Article  CAS  Google Scholar 

  18. Long H, Liao Z, Wang Y, Liao L, Lai W. Efficacy of botulinum toxins on bruxism: an evidence-based review. Int Dent J. 2012;62(1):1–5.

    Article  PubMed  Google Scholar 

  19. Kollewe K, Mohammadi B, Köhler S, Pickenbrock H, Dengler R, Dressler D. Blepharospasm: long-term treatment with either Botox®, Xeomin® or Dysport®. J Neural Transm. 2015;122(3):427–31.

    Article  CAS  PubMed  Google Scholar 

  20. Elston JS. Botulinum toxin treatment of hemifacial spasm. J Neurol Neurosurg Psychiatry. 1986;49(7):827–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Oh H-M, Chung ME. Botulinum toxin for neuropathic pain: a review of the literature. Toxins (Basel). 2015;7(8):3127–54. This article discusses recent advances in botulinum toxin therapy for pain. It discusses recent mechanistic insights and summarizes both clinical and experimental evidence for the use of botulinum toxin to treat pain. The illustrated figure discussing the mechanism of peripheral and central nervous system sensitization included in this manuscript is especially useful.

    Article  Google Scholar 

  22. Bach-Rojecky L, Salković-Petrisić M, Lacković Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010;633(1–3):10–4.

    Article  CAS  PubMed  Google Scholar 

  23. Emad MR, Emad M, Taheri P. The efficacy of intradermal injection of botulinum toxin in patients with post-herpetic neuralgia. Iran Red Crescent Med J. 2011;13(5):323–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Ngeow WC, Nair R. Injection of botulinum toxin type A (BOTOX) into trigger zone of trigeminal neuralgia as a means to control pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109(3):e47–50.

    Article  PubMed  Google Scholar 

  25. Taylor M, Silva S, Cottrell C. Botulinum toxin type-A (BOTOX) in the treatment of occipital neuralgia: a pilot study. Headache. 2008;48(10):1476–81.

    Article  PubMed  Google Scholar 

  26. Shaw LC, Price CIM, van Wijck FMJ, Shackley P, Steen N, Barnes MP, et al. Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial: effect on impairment, activity limitation, and pain. Stroke. 2011;42(5):1371–9.

    Article  CAS  PubMed  Google Scholar 

  27. Rath JJG, Tavy DLJ, Wertenbroek AAACM, van Woerkom TCAM, de Bruijn SFTM. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects. Parkinsonism Relat Disord. 2010;16(7):478–81.

    Article  PubMed  Google Scholar 

  28. Naumann M, Jankovic J. Safety of botulinum toxin type A: a systematic review and meta-analysis. Curr Med Res Opin. 2004;20(7):981–90.

    Article  CAS  PubMed  Google Scholar 

  29. Chang MA. Possible adverse effects of repeated botulinum toxin a injections to decrease post-stroke spasticity in adults undergoing rehabilitation: a review of the literature. J Allied Health. 2015;44(3):140–4. This manuscript discusses the complications that can arise from using botulinum toxin as a treatment therapy. This is a comprehensive review which includes a discussion of manuscripts from several scientific databases regarding the local and systemic effects of repeated botulinum toxin treatments.

    PubMed  Google Scholar 

  30. Li M, Goldberger BA, Hopkins C. Fatal case of BOTOX®-related anaphylaxis? J Forensic Sci. 2005;50(1):1–4.

    Google Scholar 

  31. Baricich A, Grana E, Carda S, Santamato A, Cisari C, Invernizzi M. High doses of onabotulinumtoxinA in post-stroke spasticity: a retrospective analysis. J Neural Transm. 2015;122(9):1283–7. This recent article sheds light on the somewhat controversial use of high-dose botulinum toxin as an effective and safe treatment for upper and lower limb post-stroke spasticity.

    Article  CAS  PubMed  Google Scholar 

  32. Nuanthaisong U, Abraham N, Goldman HB. Incidence of adverse events after high doses of onabotulinumtoxinA for multiple indications. Urology. 2014;84(5):1044–8.

    Article  PubMed  Google Scholar 

  33. Jost WH, Benecke R, Hauschke D, Jankovic J, Kaňovský P, Roggenkämper P, et al. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Drug Des Devel Ther. 2015;9:1913–26. This article is a review of data from clinical trials involving botulinum toxin as a treatment therapy. The goal of this review was to summarize data from clinical trials in order to optimize the physician’s use of botulinum toxin as a tailored treatment to individuals for specific conditions by altering the formulation, dose, and treatment intervals of the toxin.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Cernuda-Morollon E, Ramon C, Larrosa D, Alvarez R, Riesco N, Pascual J. Long-term experience with onabotulinumtoxinA in the treatment of chronic migraine: what happens after 1 year? Cephalalgia. 2014;35(10):864–8.

    Article  PubMed  Google Scholar 

  35. Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm. Pain. 2000;85(1–2):101–5.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology, Louisiana State University Health Science Center, 1542 Tulane Ave, New Orleans, LA, 70112, USA

    Shilpadevi Patil, Olga Willett, Terin Thompkins, Robert Hermann, Sathish Ramanathan, Elyse M. Cornett, Charles J. Fox & Alan David Kaye

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  1. Shilpadevi Patil
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  2. Olga Willett
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  3. Terin Thompkins
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  4. Robert Hermann
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  6. Elyse M. Cornett
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  7. Charles J. Fox
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  8. Alan David Kaye
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Correspondence to Alan David Kaye.

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Conflict of Interest

Shilpadevi Patil, Olga Willett, Terin Thompkins, Robert Hermann, Sathish Ramanathan, Elyse M. Cornett, Charles J. Fox, and Alan David Kaye declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Other Pain

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Patil, S., Willett, O., Thompkins, T. et al. Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States. Curr Pain Headache Rep 20, 15 (2016). https://doi.org/10.1007/s11916-016-0545-0

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  • DOI: https://doi.org/10.1007/s11916-016-0545-0

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