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Botox for Migraine Headaches and Facial Pain

  • Rachel Kaye
  • William J. Binder
  • Andrew Blitzer
Chapter

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.

Keywords

Trigeminal neuralgia Migraine headaches Temporomandibular joint dysfunction Chemodenervation Botulinum toxin 

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. 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.CrossRefPubMedGoogle Scholar
  2. 2.
    Kerner J. Vergiftung durch verdorbene Wü rste. Tübinger Blätter fur Naturwissenschaften und Arzneykunde. 1817;3:1–25.Google Scholar
  3. 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. 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. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Van Ermengem E. Uber einen neuen anaeroben Bacillus und seine Beziehung zum Botulismus. Z Hyg Infektionskr. 1897;26:1–56.Google Scholar
  7. 7.
    Leuchs J. Beitrage zur Kenntnis des Toxins und Antitoxins des Bacillus botulinus. Z Hyg Infektionskr. 1920;65:55–84.CrossRefGoogle Scholar
  8. 8.
    Tchitchikine A. Essai d’immunisation par la voie gastrointestinal contre la toxine botulique. Ann Inst Pasteur. 1905;xix:335.Google Scholar
  9. 9.
    Burke GS. The occurrence of Bacillus botulinus in nature. J Bacteriol. 1919;4(5):541–53.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol. 1973;12(12):924–7.PubMedGoogle Scholar
  11. 11.
    Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc. 1981;79:734–70.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Ting PT, Freiman A. The story of Clostridium botulinum: from food poisoning to Botox. Clin Med (Lond). 2004;4(3):258–61.CrossRefGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 15.
    Gimenez DF, Gimenez JA. The typing of botulinal neurotoxins. Int J Food Microbiol. 1995;27(1):1–9.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Aoki KR. Physiology and pharmacology of therapeutic botulinum neurotoxins. Curr Probl Dermatol. 2002;30:107–16.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Burstein R, et al. Extracranial origin of headache. Curr Opin Neurol. 2017;30(3):263–71.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 22.
    Selby G, Lance JW. Observations on 500 cases of migraine and allied vascular headache. J Neurol Neurosurg Psychiatry. 1960;23:23–32.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kosaras B, et al. Sensory innervation of the calvarial bones of the mouse. J Comp Neurol. 2009;515(3):331–48.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Schueler M, et al. Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache. Pain. 2013;154(9):1622–31.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Guyuron B, et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg. 2009;124(2):461–8.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Young WB. Occipital nerve stimulation for chronic migraine. Curr Pain Headache Rep. 2014;18(2):396.CrossRefPubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 33.
    Blumenfeld A, Ashkenazi A, Evans RW. Occipital and trigeminal nerve blocks for migraine. Headache. 2015;55(5):682–9.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 40.
    Jakubowski M, et al. Exploding vs. imploding headache in migraine prophylaxis with botulinum toxin A. Pain. 2006;125(3):286–95.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26(5):785–93.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 43.
    Silberstein SD, Lipton RB, Goadsby PJ. Headache in clinical practice. Oxford: Isis Medical Media; 1998.Google Scholar
  44. 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.CrossRefPubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 46.
    Cui M, et al. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107(1–2):125–33.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Mathew NT, Kaup AO. The use of botulinum toxin type A in headache treatment. Curr Treat Options Neurol. 2002;4(5):365–73.CrossRefPubMedGoogle Scholar
  49. 49.
    Obermann M, Holle D, Katsarava Z. Trigeminal neuralgia and persistent idiopathic facial pain. Expert Rev Neurother. 2011;11(11):1619–29.CrossRefPubMedGoogle Scholar
  50. 50.
    Jia DZ, Li G. Bioresonance hypothesis: a new mechanism on the pathogenesis of trigeminal neuralgia. Med Hypotheses. 2010;74(3):505–7.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefGoogle Scholar
  52. 52.
    Guardiani E, et al. A new treatment paradigm for trigeminal neuralgia using Botulinum toxin type A. Laryngoscope. 2014;124(2):413–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Cruccu G, et al. AAN-EFNS guidelines on trigeminal neuralgia management. Eur J Neurol. 2008;15(10):1013–28.CrossRefPubMedGoogle Scholar
  54. 54.
    Zakrzewska JM. Medical management of trigeminal neuropathic pains. Expert Opin Pharmacother. 2010;11(8):1239–54.CrossRefPubMedGoogle Scholar
  55. 55.
    Cruccu G, Truini A. Refractory trigeminal neuralgia. Non-surgical treatment options. CNS Drugs. 2013;27(2):91–6.CrossRefPubMedGoogle Scholar
  56. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar
  58. 58.
    Taha JM, Tew JM Jr. Treatment of trigeminal neuralgia by percutaneous radiofrequency rhizotomy. Neurosurg Clin N Am. 1997;8(1):31–9.PubMedCrossRefGoogle Scholar
  59. 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.CrossRefPubMedGoogle Scholar
  60. 60.
    Matak I, et al. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011;186:201–7.CrossRefGoogle Scholar
  61. 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.CrossRefPubMedGoogle Scholar
  62. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 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.CrossRefPubMedGoogle Scholar
  64. 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.CrossRefPubMedGoogle Scholar
  65. 65.
    Piovesan EJ, et al. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology. 2005;65(8):1306–8.CrossRefPubMedGoogle Scholar
  66. 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.CrossRefGoogle Scholar
  67. 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. 68.
    Mor N, Tang C, Blitzer A. Temporomandibular myofacial pain treated with botulinum toxin injection. Toxins (Basel). 2015;7(8):2791–800.CrossRefGoogle Scholar
  69. 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.CrossRefPubMedGoogle Scholar
  70. 70.
    Patel AA, Lerner MZ, Blitzer A. IncobotulinumtoxinA injection for temporomandibular joint disorder. Ann Otol Rhinol Laryngol. 2017;126(4):328–33.CrossRefPubMedGoogle Scholar
  71. 71.
    Shilpa PS, et al. Botulinum toxin: The Midas touch. J Nat Sci Biol Med. 2014;5(1):8–14.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 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.CrossRefGoogle Scholar
  73. 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.CrossRefPubMedGoogle Scholar
  74. 74.
    Schwartz M, Freund B. Treatment of temporomandibular disorders with botulinum toxin. Clin J Pain. 2002;18(6 Suppl):S198–203.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Rachel Kaye
    • 1
    • 2
  • William J. Binder
    • 3
    • 4
  • Andrew Blitzer
    • 1
    • 2
    • 5
    • 6
    • 7
  1. 1.Rutgers New Jersey Medical SchoolNewarkUSA
  2. 2.New York Center for Voice and Swallowing DisordersNew YorkUSA
  3. 3.David Geffen School of MedicineLos AngelesUSA
  4. 4.Department of Head and Neck SurgeryUniversity of California-Los AngelesLos AngelesUSA
  5. 5.Head and Neck Surgical GroupNew YorkUSA
  6. 6.Department of Otolaryngology-Head and Neck SurgeryColumbia University College of Physicians and SurgeonsNew YorkUSA
  7. 7.Department of OtolaryngologyIcahn School of Medicine at Mt. SinaiNew YorkUSA

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