Skip to main content
SpringerLink
Log in

Botox for Migraine Headaches and Facial Pain

  • Chapter
  • First Online:
Diagnosis and Management of Head and Face Pain

Abstract

Botulinum toxin has existed for thousands of years in the natural world, although investigations into its therapeutic use began in earnest in the late 1970s. It has been implicated in many different mechanisms in reducing inflammation and nociception, including central desensitization, inhibition of nociceptor expression, and inhibition of nociceptive and inflammatory neuropeptides and neurotransmitters. Due to its safety and efficacy in reducing neurogenic and musculoskeletal pain, it has been investigated in multiple pain syndromes, including migraine headaches, trigeminal neuralgia, and temporomandibular joint dysfunction. Botulinum toxin has been shown to be a useful and safe adjunct in the treatment for these disorders and may reduce or eliminate oral pharmacotherapy. We present the historical background, development, proposed mechanisms of action, uses, and techniques for administering botulinum toxin for these disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BoNT:

Botulinum neurotoxin

BoNT-A:

Botulinum neurotoxin type A

BoNT-B:

Botulinum neurotoxin type B

CGRP:

Calcitonin gene-related peptide

FDA:

US Food and Drug Administration

HA:

Headache

NSF:

N-ethylmaleimide-sensitive factor

SNAP:

Soluble NSF attachment protein

SNARE:

Soluble NSF attachment protein receptor

TMD:

Temporomandibular disorder

TN:

Trigeminal neuralgia

TRPV1:

Transient receptor potential vanilloid subfamily member 1

VAMP:

Vesicular-associated membrane protein

References

  1. Erbguth FJ. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord. 2004;19(Suppl 8):S2–6.

    Article  PubMed  Google Scholar 

  2. Kerner J. Vergiftung durch verdorbene Wü rste. Tübinger Blätter fur Naturwissenschaften und Arzneykunde. 1817;3:1–25.

    Google Scholar 

  3. Kerner J. Neue Beobachtungen uber die in Wurttemberg so haufig vorfallenden todlichen Vergiftungen durch den Genuss geraucherter Wurste. Osiander: Tubingen; 1820.

    Google Scholar 

  4. Kerner J. Das Fettgift oder die Fettsaure und ihre Wirkungen auf den thierischen Organismus, ein Beytrag zur Untersuchung des in verdorbenen Wursten giftig wirkenden Stoffes. Cotta: Stuttgart; 1822.

    Google Scholar 

  5. Erbguth FJ, Naumann M. On the first systematic descriptions of botulism and botulinum toxin by Justinus Kerner (1786-1862). J Hist Neurosci. 2000;9(2):218–20.

    Article  CAS  PubMed  Google Scholar 

  6. Van Ermengem E. Uber einen neuen anaeroben Bacillus und seine Beziehung zum Botulismus. Z Hyg Infektionskr. 1897;26:1–56.

    Google Scholar 

  7. Leuchs J. Beitrage zur Kenntnis des Toxins und Antitoxins des Bacillus botulinus. Z Hyg Infektionskr. 1920;65:55–84.

    Article  Google Scholar 

  8. Tchitchikine A. Essai d’immunisation par la voie gastrointestinal contre la toxine botulique. Ann Inst Pasteur. 1905;xix:335.

    Google Scholar 

  9. Burke GS. The occurrence of Bacillus botulinus in nature. J Bacteriol. 1919;4(5):541–53.

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol. 1973;12(12):924–7.

    PubMed  CAS  Google Scholar 

  11. Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc. 1981;79:734–70.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Ting PT, Freiman A. The story of Clostridium botulinum: from food poisoning to Botox. Clin Med (Lond). 2004;4(3):258–61.

    Article  Google Scholar 

  13. Lew MF, Brashear A, Factor S. The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: summary of three controlled clinical trials. Neurology. 2000;55(12 Suppl 5):S29–35.

    PubMed  CAS  Google Scholar 

  14. Benecke R, et al. A new botulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949–51.

    Article  CAS  PubMed  Google Scholar 

  15. Gimenez DF, Gimenez JA. The typing of botulinal neurotoxins. Int J Food Microbiol. 1995;27(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  16. Arndt JW, et al. A structural perspective of the sequence variability within botulinum neurotoxin subtypes A1-A4. J Mol Biol. 2006;362(4):733–42.

    Article  CAS  PubMed  Google Scholar 

  17. Whitemarsh RC, et al. Characterization of botulinum neurotoxin A subtypes 1 through 5 by investigation of activities in mice, in neuronal cell cultures, and in vitro. Infect Immun. 2013;81(10):3894–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Aoki KR. Physiology and pharmacology of therapeutic botulinum neurotoxins. Curr Probl Dermatol. 2002;30:107–16.

    Article  CAS  PubMed  Google Scholar 

  19. Sutton RB, et al. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature. 1998;395(6700):347–53.

    Article  CAS  PubMed  Google Scholar 

  20. Burstein R, et al. Extracranial origin of headache. Curr Opin Neurol. 2017;30(3):263–71.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wolff HG, Tunis MM, Goodell H. Studies on headache; evidence of damage and changes in pain sensitivity in subjects with vascular headaches of the migraine type. AMA Arch Intern Med. 1953;92(4):478–84.

    Article  CAS  PubMed  Google Scholar 

  22. Selby G, Lance JW. Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry. 1960;23:23–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kosaras B, et al. Sensory innervation of the calvarial bones of the mouse. J Comp Neurol. 2009;515(3):331–48.

    PubMed  PubMed Central  Google Scholar 

  24. Schueler M, et al. Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache. Pain. 2013;154(9):1622–31.

    Article  PubMed  Google Scholar 

  25. Schueler M, et al. Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents. Headache. 2014;54(6):996–1009.

    Article  PubMed  Google Scholar 

  26. Perry CJ, et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications for extracranial origin of headache. Ann Neurol. 2016;79(6):1000–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Janis JE, et al. A review of current evidence in the surgical treatment of migraine headaches. Plast Reconstr Surg. 2014;134(4 Suppl 2):131S–41S.

    Article  CAS  PubMed  Google Scholar 

  28. Chepla KJ, Oh E, Guyuron B. Clinical outcomes following supraorbital foraminotomy for treatment of frontal migraine headache. Plast Reconstr Surg. 2012;129(4):656e–62e.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Guyuron B, et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg. 2009;124(2):461–8.

    Article  CAS  PubMed  Google Scholar 

  30. Saper JR, et al. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalalgia. 2011;31(3):271–85.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Young WB. Occipital nerve stimulation for chronic migraine. Curr Pain Headache Rep. 2014;18(2):396.

    Article  PubMed  Google Scholar 

  32. Dach F, et al. Nerve block for the treatment of headaches and cranial neuralgias—a practical approach. Headache. 2015;55 Suppl 1:59–71.

    Article  PubMed  Google Scholar 

  33. Blumenfeld A, Ashkenazi A, Evans RW. Occipital and trigeminal nerve blocks for migraine. Headache. 2015;55(5):682–9.

    Article  PubMed  Google Scholar 

  34. Binder WJ, et al. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg. 2000;123(6):669–76.

    Article  CAS  PubMed  Google Scholar 

  35. Ondo WG, Vuong KD, Derman HS. Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia. 2004;24(1):60–5.

    Article  CAS  PubMed  Google Scholar 

  36. Silberstein S, et al. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache. 2000;40(6):445–50.

    Article  CAS  PubMed  Google Scholar 

  37. Tepper SJ, et al. Botulinum neurotoxin type A in the preventive treatment of refractory headache: a review of 100 consecutive cases. Headache. 2004;44(8):794–800.

    Article  PubMed  Google Scholar 

  38. Dodick DW, et al. Botulinum toxin type a for the prophylaxis of chronic daily headache: subgroup analysis of patients not receiving other prophylactic medications: a randomized double-blind, placebo-controlled study. Headache. 2005;45(4):315–24.

    Article  PubMed  Google Scholar 

  39. Evers S, et al. Botulinum toxin A in the prophylactic treatment of migraine—a randomized, double-blind, placebo-controlled study. Cephalalgia. 2004;24(10):838–43.

    Article  CAS  PubMed  Google Scholar 

  40. Jakubowski M, et al. Exploding vs. imploding headache in migraine prophylaxis with botulinum toxin A. Pain. 2006;125(3):286–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26(5):785–93.

    Article  CAS  PubMed  Google Scholar 

  42. Brin MF, et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov Disord. 1987;2(4):237–54.

    Article  CAS  PubMed  Google Scholar 

  43. Silberstein SD, Lipton RB, Goadsby PJ. Headache in clinical practice. Oxford: Isis Medical Media; 1998.

    Google Scholar 

  44. Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon. 2000;38(2):245–58.

    Article  CAS  PubMed  Google Scholar 

  45. Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004;44(1):35–42; discussion 42–3.

    Article  PubMed  Google Scholar 

  46. Cui M, et al. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107(1–2):125–33.

    Article  CAS  PubMed  Google Scholar 

  47. Blumenfeld AM, et al. Insights into the functional anatomy behind the PREEMPT injection paradigm: guidance on achieving optimal outcomes. Headache. 2017;57(5):766–77.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mathew NT, Kaup AO. The use of botulinum toxin type A in headache treatment. Curr Treat Options Neurol. 2002;4(5):365–73.

    Article  PubMed  Google Scholar 

  49. Obermann M, Holle D, Katsarava Z. Trigeminal neuralgia and persistent idiopathic facial pain. Expert Rev Neurother. 2011;11(11):1619–29.

    Article  PubMed  Google Scholar 

  50. Jia DZ, Li G. Bioresonance hypothesis: a new mechanism on the pathogenesis of trigeminal neuralgia. Med Hypotheses. 2010;74(3):505–7.

    Article  PubMed  Google Scholar 

  51. Garza I, et al. Headache and other craniofacial pain. In: Daroff R, et al., editors. Bradley’s neurology in clinical practice. 6th ed. Philadelphia: Elsevier; 2012. p. 1703–44.

    Chapter  Google Scholar 

  52. Guardiani E, et al. A new treatment paradigm for trigeminal neuralgia using Botulinum toxin type A. Laryngoscope. 2014;124(2):413–7.

    Article  CAS  PubMed  Google Scholar 

  53. Cruccu G, et al. AAN-EFNS guidelines on trigeminal neuralgia management. Eur J Neurol. 2008;15(10):1013–28.

    Article  CAS  PubMed  Google Scholar 

  54. Zakrzewska JM. Medical management of trigeminal neuropathic pains. Expert Opin Pharmacother. 2010;11(8):1239–54.

    Article  CAS  PubMed  Google Scholar 

  55. Cruccu G, Truini A. Refractory trigeminal neuralgia. Non-surgical treatment options. CNS Drugs. 2013;27(2):91–6.

    Article  PubMed  Google Scholar 

  56. Morra ME, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Bond AE, et al. Operative strategies for minimizing hearing loss and other major complications associated with microvascular decompression for trigeminal neuralgia. World Neurosurg. 2010;74(1):172–7.

    Article  PubMed  Google Scholar 

  58. Taha JM, Tew JM Jr. Treatment of trigeminal neuralgia by percutaneous radiofrequency rhizotomy. Neurosurg Clin N Am. 1997;8(1):31–9.

    Article  PubMed  CAS  Google Scholar 

  59. Xiao L, et al. Botulinum toxin type A reduces hyperalgesia and TRPV1 expression in rats with neuropathic pain. Pain Med. 2013;14(2):276–86.

    Article  PubMed  Google Scholar 

  60. Matak I, et al. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011;186:201–7.

    Article  CAS  Google Scholar 

  61. Matak I, Riederer P, Lackovic Z. Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int. 2012;61(2):236–9.

    Article  CAS  PubMed  Google Scholar 

  62. Wu C, et al. Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia. Springerplus. 2016;5:431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shimizu T, et al. Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. Neurobiol Dis. 2012;48(3):367–78.

    Article  CAS  PubMed  Google Scholar 

  64. Micheli F, Scorticati MC, Raina G. Beneficial effects of botulinum toxin type a for patients with painful tic convulsif. Clin Neuropharmacol. 2002;25(5):260–2.

    Article  PubMed  Google Scholar 

  65. Piovesan EJ, et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 2005;65(8):1306–8.

    Article  CAS  PubMed  Google Scholar 

  66. Sirois D, et al. Botulinum toxin-A in trigeminal neuralgia: outcome of placebo-controlled RCT. Oral Surg ORal Med Oral Pathol Oral Radiol Endod. 2011;112:e130.

    Article  Google Scholar 

  67. Ohrbach R, Stohler C. Diagnosis of temporomandibular disorders: a critical review of current diagnostic systems. J Cranio Disord Fac Oral Pain. 1992;6(4):307–17.

    Google Scholar 

  68. Mor N, Tang C, Blitzer A. Temporomandibular myofacial pain treated with botulinum toxin injection. Toxins (Basel). 2015;7(8):2791–800.

    Article  CAS  Google Scholar 

  69. Song PC, Schwartz J, Blitzer A. The emerging role of botulinum toxin in the treatment of temporomandibular disorders. Oral Dis. 2007;13(3):253–60.

    Article  CAS  PubMed  Google Scholar 

  70. Patel AA, Lerner MZ, Blitzer A. IncobotulinumtoxinA injection for temporomandibular joint disorder. Ann Otol Rhinol Laryngol. 2017;126(4):328–33.

    Article  PubMed  Google Scholar 

  71. Shilpa PS, et al. Botulinum toxin: The Midas touch. J Nat Sci Biol Med. 2014;5(1):8–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Bossowska A, et al. Botulinum toxin type A induces changes in the chemical coding of substance P-immunoreactive dorsal root ganglia sensory neurons supplying the porcine urinary bladder. Toxins (Basel). 2015;7(11):4797–816.

    Article  CAS  Google Scholar 

  73. Freund BJ, Schwartz M. Relief of tension-type headache symptoms in subjects with temporomandibular disorders treated with botulinum toxin-A. Headache. 2002;42(10):1033–7.

    Article  PubMed  Google Scholar 

  74. Schwartz M, Freund B. Treatment of temporomandibular disorders with botulinum toxin. Clin J Pain. 2002;18(6 Suppl):S198–203.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rutgers New Jersey Medical School, Newark, NJ, USA

    Rachel Kaye & Andrew Blitzer

  2. New York Center for Voice and Swallowing Disorders, New York, NY, USA

    Rachel Kaye & Andrew Blitzer

  3. David Geffen School of Medicine, Los Angeles, CA, USA

    William J. Binder

  4. Department of Head and Neck Surgery, University of California-Los Angeles, Los Angeles, CA, USA

    William J. Binder

  5. Head and Neck Surgical Group, New York, NY, USA

    Andrew Blitzer

  6. Department of Otolaryngology-Head and Neck Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Andrew Blitzer

  7. Department of Otolaryngology, Icahn School of Medicine at Mt. Sinai, New York, NY, USA

    Andrew Blitzer

Authors
  1. Rachel Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William J. Binder
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew Blitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Otolaryngology-HNS, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    James Y. Suen

  2. Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Erika Petersen

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kaye, R., Binder, W.J., Blitzer, A. (2018). Botox for Migraine Headaches and Facial Pain. In: Suen, J., Petersen, E. (eds) Diagnosis and Management of Head and Face Pain. Springer, Cham. https://doi.org/10.1007/978-3-319-90999-8_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90999-8_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90998-1

  • Online ISBN: 978-3-319-90999-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation