Skip to main content

Advertisement

SpringerLink
Log in

Non-Invasive Neuromodulation for Headache Disorders

  • Headache (R. B. Halker, Section Editor)
  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

Migraine and other chronic headache disorders are common and if inadequately treated, can lead to significant disability. The effectiveness of medications can be limited by side effects, drug interactions, and comorbid diseases necessitating alternative methods. Technological developments in the past 5 years have made it possible to use non-invasive methods of neuromodulation to treat primary headache disorders. This field includes technologies such as supraorbital transcutaneous stimulation (STS), transcranial magnetic stimulation (TMS), and non-invasive vagal nerve stimulation (nVNS). Existing trials show these modalities are safe and well tolerated and can be combined with standard pharmacotherapy. We review the technologies, biological rationales, and trials involving non-invasive neuromodulation for the treatment of primary headache disorders.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

  1. Lipton R, Stewart W, Diamond S, Diamond M, Reed M. Prevalence and burden of migraine in the United States: data from the American migraine study II. Headache. 2001;41:646–57.

    Article  CAS  PubMed  Google Scholar 

  2. Hepp Z, Dodick D, Varon S, Gillard P, Hansen R, Devine E. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2014;35:478–88.

    Article  PubMed  Google Scholar 

  3. The international classification of headache disorders, 3rd edition (beta version). Cephalagia 2013;33:629-808.

  4. Manack A, Buse D, Lipton R. Chronic migraine: epidemiology and disease burden. Curr Pain Headache Rep. 2011;15:70–8.

    Article  PubMed  Google Scholar 

  5. Ramadan N. The link between glutamate and migraine. CNS Spectr. 2003;8:446–9.

    Article  PubMed  Google Scholar 

  6. Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz M. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59:652–61.

    Article  CAS  PubMed  Google Scholar 

  7. Schwedt T, Dodick D, Hentz J, Trentman T, Zimmerman R. Occipital nerve stimulation for chronic headache—long-term safety and efficacy. Cephalalgia. 2007;27:153–7.

    Article  CAS  PubMed  Google Scholar 

  8. Saper J, Dodick D, Silberstein S, McCarville S, Sun M, Goadsby P. Occipital nerve stimulation for the treatment of intractable chronic migraine headache: ONSTIM feasibility study. Cephalagia. 2010;31:271–85.

    Article  Google Scholar 

  9. Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation in patients with thalamic pain. J Neurosurg. 1993;78:393–401.

    Article  CAS  PubMed  Google Scholar 

  10. Fontaine D, Lazorthes Y, Mertens P, et al. Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension. J Headache Pain. 2010;11:23–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Schoenen J, Clemente LD, vanderheede M, et al. Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain. 2005;128:940–7.

    Article  CAS  PubMed  Google Scholar 

  12. Coughlin A, Badura A, Fleisher T, Guck T. Multidisciplinary treatment of chronic pain patients: its efficacy in changing patient locus of control. Arch Phys Med Rehabil. 2000;81:739–40.

    Article  CAS  PubMed  Google Scholar 

  13. Lefaucheur J, Andre-Obadia N, Antal A, Ayache S, Baeken C, Benninger D. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation. Clin Neurophys. 2014;125:2150–206.

    Article  Google Scholar 

  14. Narayana S, Papanicolaou A, McGregor A, Boop F, Wheless J. Clinical applications of transcranial magnetic stimulation in pediatric neurology. J Child Neurol. 2014;30:1111–24.

    Article  PubMed  Google Scholar 

  15. Solomon S, Guglielmo K. Treatment of headache by transcutaneous electrical stimulation. Headache. 1985;25:12–5.

    Article  CAS  PubMed  Google Scholar 

  16. Tayeb Z, Hafeez F, Shafiq Q. Successful treatment of nummular headache with TENS. Cephalalgia. 2008;28:897–8.

    Article  CAS  PubMed  Google Scholar 

  17. Cruccu G, Aziz T, Garcia-Larresa L, et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol. 2007;14:952–70.

    Article  CAS  PubMed  Google Scholar 

  18. Sluka K, Judge M, McColley M, Reveiz P, Taylor B. Low frequency TENS is less effective than high frequency TENS at reducing inflammtion-induced hyperalgesia in morphone-tolerant rats. Eur J Pain. 2000;4:185–93.

    Article  CAS  PubMed  Google Scholar 

  19. Piquet M, Balestra C, Sava S, Schoenen J. Supraorbital transcutaneous neurostimulation has sedative effects in healthy subjects. BMC Neurol. 2011;11:135. This study showed the device to be safe for use in healthy volunteers with verum stimulation leading to mild sedative effects.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Craig A. Spinal and trigeminal lamina I input to the locus coeruleus anterogradely labeled with phaseolus vulgaris leucoagglutinin (PHA-L) in the cat and the monkey. Brain Res. 1992;584:325–8.

    Article  CAS  PubMed  Google Scholar 

  21. Schoenen J, Vandersmissen B, Jeangette S, et al. Migraine prevention with a supraorbital transcutaneous stimulator. Neurology. 2013;80:697–704. Double-blind, RTC, sham-controlled study for STS as a migraine preventive. Significantly reduced headache days at three months of use though did not reduce headache severity.

    Article  PubMed  Google Scholar 

  22. Magis D, Sava S, D'Elia T, Schoenen J. Safety and patients’ satisfaction of transcutaneous supraorbital neuroStimulation (tSNS) with the Cefaly® device in headache treatment: a survey of 2,313 headache sufferers in the general population. J Headache Pain. 2013;14:95.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Anand S, Hotson J. Transcranial magnetic stimulation: neurophysiological applications and safety. Brain and Cogn. 2002;50:366–86.

    Article  Google Scholar 

  24. Rossini P, Rossi S. Transcranial magnetic stimulation: diagnostic, therapeutic and research potential. Neurology. 2007;68:484–8.

    Article  PubMed  Google Scholar 

  25. Wasserman E. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial magnetic Stimulation, June 5–7, 1996. Electroencephalogr Clin Neurophysiol. 1997;108:1–16.

    Article  Google Scholar 

  26. Dodick D, Schembri C, Helmuth M, Aurora S. Transcranial magnetic stimulation for migraine: a safety review. Headache. 2010;50:1153–63.

    Article  PubMed  Google Scholar 

  27. Lipton R, Dodick D, Silberstein S, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurology. 2010;9:373–80. Double-blind, RTC, sham-controlled study for TMS as abortive migraine treatment. Treatment group more likely to be pain free at 372 h but no differences seen in abortive medication use.

    Article  PubMed  Google Scholar 

  28. Almaraz A, Dilli E, Dodick D. The effect of prophylactic medications on TMS for migraine aura. Headache Curr. 2010;50:1630–3.

    Article  Google Scholar 

  29. Bhola R, Kinsella E, Giffin N, et al. Single-pulse transcranial magnetic stimulation (sTMS) for the acute treatment of migraine: evaluation of outcome data for the UK post market pilot program. J Headache Pain. 2015;16:51.

    Article  PubMed Central  Google Scholar 

  30. Sadler R, Purdy R, Rahey S. Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalagia. 2002;22:482–4.

    Article  CAS  Google Scholar 

  31. Hord E, Evans M, Mueed S, Adamolekun B, Naritoku D. The effect of vagus nerve stimulation on migraines. J Pain. 2003;4:530–4.

    Article  PubMed  Google Scholar 

  32. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalagia. 2005;25:82–6.

    Article  CAS  Google Scholar 

  33. Cecchini A, Mea E, Tullo V, et al. Vagus nerve stimulation in drug-resistant daily chronic migraine with depression: preliminary data. Neurol Sci 2009;30.

  34. Kirchner A, Birklein F, Stefan H, Handwerker H. Left vagus nerve stimulation suppresses experimentally induced pain. Neurology. 2000;55:1167–71.

    Article  CAS  PubMed  Google Scholar 

  35. Bohotin C, Scholsem M, Multon S, Martin D, Bohotin V, Schoenen J. Vagus nerve stimulation in awake rats reduces formalin-induced nociceptive behaviour and fos-immunoreactivity in trigeminal nucleus caudalis. Pain. 2003;101:3–12.

    Article  CAS  PubMed  Google Scholar 

  36. Oshinsky M, Murphy A, Hekierski H, Cooper M, Simon B. Non-invasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain. 2014;155:1037–42.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Schachter S, Saper C. Progress in epilepsy research: vagus nerve stimulation. Epilepsia. 1998;39:677–86.

    Article  CAS  PubMed  Google Scholar 

  38. Ferrari GD, Crijns H, Borggrefe M, et al. Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2011;32:857–5.

    Article  Google Scholar 

  39. Sjogren M, Hellstrom P, Jonsson M, Runngerstam M, Silander H, Ben-Menachem E. Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psych. 2002;63:972–80.

    Article  Google Scholar 

  40. Silberstein S. Non-invasive vagus nerve stimulation in the treatment of migraine headache. Presented at the 4th European Headache and Migraine Trust International Congress; September 20, 2014; Copenhagen, Denmark.

  41. Silberstein S, Silva AD, Calhoun A, Grosberg B, Lipton R, Cady R. Non-invasive vagus nerve stimulation for chronic migraine prevention in a prospective, randomized, sham-controlled pilot study (the EVENT Study): report from the double-blind phase. Presented at the 56th Annual Scientific Meeting of the American Headache Society; June 2014; Los Angeles, California. Double-blind, RTC, sham-controlled study for nVNS as migraine preventive. Reduced number of migraine days with more benefits seen after multiple months of use.

  42. Silberstein S, Silva AD, Calhoun A, Grosberg B, Lipton R, Cady R. Non-invasive vagus nerve stimulation for chronic migraine prevention in a prospective, randomized, sham-controlled pilot Study (the EVENT Study): report from the open-label phase. Presented at the 56th Annual Scientific Meeting of the American Headache Society; June 2014; Los Angeles, California.

  43. Gaul C, Diener H, Solbach K, et al. Non-invasive vagus nerve stimulation using gammaCore® for the prevention and acute treatment of chronic cluster headache: report from the randomised phase of the PREVA study. Presented at the 4th European Headache and Migraine Trust International Congress; September 18–21, 2014; Copenhagen, Denmark. RCT, open-label study for nVNS as abortive and preventive in chronic cluster. Cluster preventive and abortive. Reduced number of headache days after 2 weeks.

  44. Gaul C, Diener H, Solbach K, et al. Non-invasive vagus nerve stimulation using gammaCore for the prevention and acute treatment of chronic cluster headache: report from the open-label phase of the PREVA study. Presented at the 4th European Headache and Migraine Trust International Congress; September 18–21, 2014; Copenhagen, Denmark.

  45. Silberstein S, Mechtler L, Kudrow D, et al. Efficacy and safety outcomes of non-invasive vagus nerve stimulation for the acute treatment (ACT1) of cluster headache study. Presented at the 57th Annual Scientific Meeting of the American Headache Society; Jun 18–21, 2015; Washington DC.

  46. Nesbitt A, Martin J, Tompkins E, Ruttledge M, Goadsby P. Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment. Neurology. 2015;84:1249–53.

    Article  CAS  PubMed  Google Scholar 

  47. Grazzi L, Padovan A, Barbanti P. Role of neurostimulation in migraine. Neurol Sci. 2015;36 Suppl 1:S121–3.

    Article  Google Scholar 

  48. Goadsby P, Grosberg B, Mauskop A, Cady R, Simmons K. Effect of noninvasive vagus nerve stimulation on acute migraine: an open label pilot study. Cephalagia. 2014;34:986–93.

    Article  CAS  Google Scholar 

  49. Rainero I, Martino PD, Rubino E, Vaula G, Gentile S, Pinessi L. Non-invasive vagal nerve stimulation for the treatment of headache attacks in patients with chronic migraine and medication-overuse headache. Neurology 2014;82:P1.262.

  50. Keskin E, Onur O, Keskin H, Gamus I, Kafali H, Turhan N. Transcutaneous electrical nerve stimulation improves low back pain during pregnancy. Gynecol Obstet Investig. 2012;74:76–83.

    Article  CAS  Google Scholar 

  51. Husain M, Stegman D, Trevino K. Pregnancy and delivery while receiving vagus nerve stimulation for the treatment of major depression: a case report. Ann Gen Psych. 2005;4:1–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Jefferson Headache Center, 900 Walnut Street, Suite 200, Philadelphia, PA, 19107, USA

    Shuhan Zhu & Michael J. Marmura

Authors
  1. Shuhan Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Marmura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Marmura.

Ethics declarations

Conflict of Interest

Shuhan Zhu declares no potential conflicts of interest.

Michael J. Marmura reports grants from eNeura and Teva.

Human and Animal Rights and Informed Consent

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

Additional information

This article is part of the Topical Collection on Headache

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhu, S., Marmura, M.J. Non-Invasive Neuromodulation for Headache Disorders. Curr Neurol Neurosci Rep 16, 11 (2016). https://doi.org/10.1007/s11910-015-0620-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11910-015-0620-7

Keywords

Search

Navigation