Skip to main content

Advertisement

SpringerLink
Log in

Transcutaneous Vagus Nerve Stimulation: an Alternative Treatment of Chronic Migraine—a Systematic Review

  • Review
  • Published:
SN Comprehensive Clinical Medicine Aims and scope Submit manuscript

Abstract

Migraine is a disabling condition that is currently underdiagnosed and undertreated. Transcutaneous vagus nerve stimulation (VNS) is among the most researched non-invasive brain stimulation techniques for migraine control. In this systematic review, we discuss the effects of VNS parameters (waveform, frequency, intensity, cycle, and current) and central and clinical mechanisms in auricular (taVNS) or cervical (tcVNS) transcutaneous VNS in the control of migraine pain. PubMed (National Library of Medicine), Cochrane Library, CAPES Journals (Portal of Journals of the Coordination for the Improvement of Higher Education Personnel), Virtual Health Library (VHL), and Google Scholar were searched by computer from the establishment of within the 10-year period (2011– 2021). Initially, a total of 10,017 articles were identified. After applying the exclusion criteria, 10,007 articles were excluded. The eligibility criteria were analyzed and only ten articles fulfilled the criteria. The most used parameters in this study for VNS were the frequencies of 1 Hz, 25 Hz, and 30 Hz. The 1-Hz stimulation caused a more significant reduction in the number of days with headache. The total stimulation time varies between studies, ranging from 2 to 240 min, and can be repeated for a period or a single session. Studies that used a longer treatment period showed clinical results in reducing pain and analyzed the scores. Moreover, studies have shown reduced intensity or severity of pain after taVNS. The studies performed taVNS or tcVNS, and both methods had positive effects on migraine control, pain reduction, and migraine score.

Key Message

An systematic literature review of transcutaneous vagus nerve stimulation (tVNS) on migraine pain management. The results indicate that auricular or cervical tVNS methods had positive effects on migraine control, pain reduction, and migraine score.

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

Fig. 1

Similar content being viewed by others

Data availability

Not applicable.

Code Availability

Not applicable.

References

  1. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622.

    Google Scholar 

  2. Steiner TJ, Birbeck GL, Jensen RH, Katsarava Z, Stovner LJ, Martelletti P. Headache disorders are third cause of disability worldwide. J Headache Pain. 2015;16:58.

    Google Scholar 

  3. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet. 2016;388(10053):1545–602.

    Google Scholar 

  4. Deneris A, Rosati Allen P, Hart Hayes E, Latendresse G. Migraines in women: current evidence for management of episodic and chronic migraines. J Midwifery Womens Health. 2017;62(3):270–85.

    Google Scholar 

  5. Viana M, Sances G, Ghiotto N, Guaschino E, Allena M, Nappi G, et al. Variability of the characteristics of a migraine attack within patients. Cephalalgia. 2016;36(9):825–30.

    CAS  Google Scholar 

  6. Katsarava Z, Manack A, Yoon MS, Obermann M, Becker H, Dommes P, et al. Chronic migraine: classification and comparisons. Cephalalgia. 2011;31(5):520–9.

    CAS  Google Scholar 

  7. Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, et al. EFNS guideline on the drug treatment of migraine–revised report of an EFNS task force. Eur J Neurol. 2009;16(9):968–81.

    CAS  Google Scholar 

  8. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337–45.

    CAS  Google Scholar 

  9. Magis D. Neuromodulation in migraine: state of the art and perspectives. Expert Rev Med Devices. 2015;12(3):329–39.

    CAS  Google Scholar 

  10. Schoenen J, Roberta B, Magis D, Coppola G. Noninvasive neurostimulation methods for migraine therapy: the available evidence. Cephalalgia. 2016;36(12):1170–80.

    Google Scholar 

  11. Driessen AK. Vagal afferent processing by the paratrigeminal nucleus. Front Physiol. 2019;10:1110.

    Google Scholar 

  12. Henssen D, Derks B, van Doorn M, Verhoogt N, Cappellen Van, van Walsum AM, Staats P, et al. Vagus nerve stimulation for primary headache disorders: an anatomical review to explain a clinical phenomenon. Cephalalgia. 2019;39(9):1180–94.

    Google Scholar 

  13. Coppola G, Vandenheede M, Di Clemente L, Ambrosini A, Fumal A, De Pasqua V, et al. Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical activity are decreased in migraine patients between attacks. Brain. 2005;128(Pt 1):98–103.

    Google Scholar 

  14. Yap JYY, Keatch C, Lambert E, Woods W, Stoddart PR, Kameneva T. Critical review of transcutaneous vagus nerve stimulation: challenges for translation to clinical practice. Front Neurosci. 2020;14:284.

    Google Scholar 

  15. Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, et al. Noninvasive vagus nerve stimulation as acute therapy for migraine: the randomized PRESTO study. Neurology. 2018;91(4):e364–73.

    Google Scholar 

  16. Hord ED, Evans MS, Mueed S, Adamolekun B, Naritoku DK. The effect of vagus nerve stimulation on migraines. J Pain. 2003;4(9):530–4.

    Google Scholar 

  17. Mosqueira AJ, López-Manzanares L, Canneti B, Barroso A, García-Navarrete E, Valdivia A, et al. Vagus nerve stimulation in patients with migraine. Rev Neurol. 2013;57(2):57–63.

    Google Scholar 

  18. Yuan H, Silberstein SD. Vagus nerve and vagus nerve stimulation, a comprehensive review: Part I. Headache. 2016;56(1):71–8.

    Google Scholar 

  19. Yuan H, Silberstein SD. Vagus nerve stimulation and headache. Headache. 2017;57(Suppl 1):29–33.

    Google Scholar 

  20. Goadsby PJ, Grosberg BM, Mauskop A, Cady R, Simmons KA. Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study. Cephalalgia. 2014;34(12):986–93.

    CAS  Google Scholar 

  21. Straube A, Ellrich J, Eren O, Blum B, Ruscheweyh R. Treatment of chronic migraine with transcutaneous stimulation of the auricular branch of the vagal nerve (auricular t-VNS): a randomized, monocentric clinical trial. J Headache Pain. 2015;16:543.

    Google Scholar 

  22. Grazzi L, Usai S, Bussone G. EHMTI-0036. GammaCore device for treatment of migraine attack: preliminary report. J Headache Pain. 2014;15(Suppl 1):G12-G.

  23. Grazzi L, Egeo G, Calhoun AH, McClure CK, Liebler E, Barbanti P. Non-invasive vagus nerve stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study. J Headache Pain. 2016;17(1):91.

    Google Scholar 

  24. Barbanti P, Grazzi L, Egeo G, Padovan AM, Liebler E, Bussone G. Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study. J Headache Pain. 2015;16:61.

    Google Scholar 

  25. Kinfe TM, Pintea B, Muhammad S, Zaremba S, Roeske S, Simon BJ, et al. Cervical non-invasive vagus nerve stimulation (nVNS) for preventive and acute treatment of episodic and chronic migraine and migraine-associated sleep disturbance: a prospective observational cohort study. J Headache Pain. 2015;16:101.

    Google Scholar 

  26. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Google Scholar 

  27. Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C. Gender-related differences in migraine. Neurol Sci. 2020;41(2):429–36.

    Google Scholar 

  28. Baksa D, Gecse K, Kumar S, Toth Z, Gal Z, Gonda X, et al. Circadian variation of migraine attack onset: a review of clinical studies. Biomed Res Int. 2019;2019:4616417.

    Google Scholar 

  29. Broner SW, Bobker S, Klebanoff L. Migraine in women. Semin Neurol. 2017;37(6):601–10.

    Google Scholar 

  30. Wijeratne T, Tang HM, Crewther D, Crewther S. Prevalence of migraine in the elderly: a narrated review. Neuroepidemiology. 2019;52(1–2):104–10.

    Google Scholar 

  31. Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, et al. Safety and tolerability of transcutaneous vagus nerve stimulation in humans; a systematic review. Brain Stimul. 2018;11(6):1225–38.

    CAS  Google Scholar 

  32. Diener H-C, Holle-Lee D, Nägel S, Dresler T, Gaul C, Göbel H, et al. Treatment of migraine attacks and prevention of migraine: guidelines by the German Migraine and Headache Society and the German Society of Neurology. Clinical and Translational Neuroscience. 2019;3(1):2514183X18823377.

    Google Scholar 

  33. Chaudhry SR, Lendvai IS, Muhammad S, Westhofen P, Kruppenbacher J, Scheef L, et al. Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): a proof-of-concept study. Brain Stimul. 2019;12(3):643–51.

    Google Scholar 

  34. Silberstein SD, Calhoun AH, Lipton RB, Grosberg BM, Cady RK, Dorlas S, et al. Chronic migraine headache prevention with noninvasive vagus nerve stimulation: the EVENT study. Neurology. 2016;87(5):529–38.

    Google Scholar 

  35. Howland RH. Vagus Nerve Stimulation. Curr Behav Neurosci Rep. 2014;1(2):64–73.

    Google Scholar 

  36. Kiyokawa J, Yamaguchi K, Okada R, Maehara T, Akita K. Origin, course and distribution of the nerves to the posterosuperior wall of the external acoustic meatus. Anatomical science international. 2014;89(4):238–45.

    Google Scholar 

  37. Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002;15(1):35–7.

    Google Scholar 

  38. Farias MMMD, Wenceslau CV, Passos J, Teixeira DG, Araújo KPC, Ambrósio CE, et al. Comportamento dos nervos glossofaríngeo e vago, na região retrofaríngea de ovinos: origem aparente no crânio, trajeto, ramificação e distribuição. Pesquisa Veterinária Brasileira. 2007;27:115–23.

    Google Scholar 

  39. Zhang Y, Liu J, Li H, Yan Z, Liu X, Cao J, et al. Transcutaneous auricular vagus nerve stimulation at 1 Hz modulates locus coeruleus activity and resting state functional connectivity in patients with migraine: An fMRI study. Neuroimage Clin. 2019;24:101971.

    Google Scholar 

  40. Cao J, Zhang Y, Li H, Yan Z, Liu X, Hou X, et al. Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine. J Transl Med. 2021;19(1):354.

    Google Scholar 

  41. Lipton RB, Stewart WF, Sawyer J, Edmeads JG. Clinical utility of an instrument assessing migraine disability: the migraine disability assessment (MIDAS) questionnaire. Headache. 2001;41(9):854–61.

    CAS  Google Scholar 

  42. Yang M, Rendas-Baum R, Varon SF, Kosinski M. Validation of the Headache Impact Test (HIT-6™) across episodic and chronic migraine. Cephalalgia an international journal of headache. 2011;31(3):357–67.

    Google Scholar 

  43. Rendas-Baum R, Bloudek LM, Maglinte GA, Varon SF. The psychometric properties of the migraine specific quality of life questionnaire version 2.1 (MSQ) in chronic migraine-patients. Qual Life Res. 2013;22(5):1123–33.

    Google Scholar 

  44. Farrahi Moghaddam J, Nakhaee N, Sheibani V, Garrusi B, Amirkafi A. Reliability and validity of the Persian version of the Pittsburgh sleep quality index (PSQI-P). Sleep Breath. 2012;16(1):79–82.

    Google Scholar 

  45. Kühner C, Bürger C, Keller F, Hautzinger M. Reliabilität und Validität des revidierten Beck-Depressionsinventars (BDI-II). Nervenarzt. 2007;78(6):651–6.

    Google Scholar 

  46. Straube A, Eren O. tVNS in the management of headache and pain. Auton Neurosci. 2021;236:102875.

    CAS  Google Scholar 

  47. Rawson FJ. New dimensions in controlling cellular function with electroceutics. Ther Deliv. 2015;6(1):5–8.

    CAS  Google Scholar 

  48. Dietrich S, Smith J, Scherzinger C, Hofmann-Preiss K, Freitag T, Eisenkolb A, et al. A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI. Biomed Tech (Berl). 2008;53(3):104–11.

    Google Scholar 

  49. Yakunina N, Kim SS, Nam EC. Optimization of transcutaneous vagus nerve stimulation using functional MRI. Neuromodulation. 2017;20(3):290–300.

    Google Scholar 

  50. Vachon-Presseau E. Effects of stress on the corticolimbic system: implications for chronic pain. Prog Neuropsychopharmacol Biol Psychiatry. 2018;87(Pt B):216–23.

    CAS  Google Scholar 

  51. Maizels M, Aurora S, Heinricher M. Beyond neurovascular: migraine as a dysfunctional neurolimbic pain network. Headache. 2012;52(10):1553–65.

    Google Scholar 

  52. Luo W, Zhang Y, Yan Z, Liu X, Hou X, Chen W, et al. The instant effects of continuous transcutaneous auricular vagus nerve stimulation at acupoints on the functional connectivity of amygdala in migraine without aura: a preliminary study. Neural Plast. 2020;2020:8870589.

    Google Scholar 

  53. Garcia RG, Lin RL, Lee J, Kim J, Barbieri R, Sclocco R, et al. Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients. Pain. 2017;158(8):1461–72.

    Google Scholar 

  54. Van Bockstaele EJ, Peoples J, Telegan P. Efferent projections of the nucleus of the solitary tract to peri-locus coeruleus dendrites in rat brain: evidence for a monosynaptic pathway. J Comp Neurol. 1999;412(3):410–28.

    Google Scholar 

  55. Akerman S, Holland PR, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci. 2011;12(10):570–84.

    CAS  Google Scholar 

  56. Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care. 2014;8(2):143–51.

    Google Scholar 

  57. Ellrich J, Messlinger K, Chiang CY, Hu JW. Modulation of neuronal activity in the nucleus raphé magnus by the 5-HT(1)-receptor agonist naratriptan in rat. Pain. 2001;90(3):227–31.

    CAS  Google Scholar 

Download references

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES)—Finance Code 001.  AFB is funded by CNPq (Grant number 305539/2021-3.

Author information

Authors and Affiliations

  1. Federal University of Alfenas, Alfenas, Minas Gerais, Brazil

    Ana Cláudia de Carvalho & Aeska Lanary Cristino Marques

  2. Biosciences Applied to Health Program, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil

    Lais Leite Ferreira

  3. Health and Function Study Nucleus, Federal University of Bahia, Salvador, Bahia, Brazil

    Francisco Xavier de Brito

  4. Center for Mathematics, Computation and Cognition, Federal University of ABC, Santo André, São Paulo, Brazil

    Abrahão Fontes Baptista

  5. Institute of Motricity Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil

    Marcelo Lourenço da Silva & Josie Resende Torres da Silva

  6. Federal University of Alfenas, LANNED, Laboratory of Neuroscience, Neuromodulation and Study of Pain, Avenida Jovino Fernandes Sales, 2600, Sala M205C, Alfenas, Minas Gerais, CEP 37133-840, Brazil

    Josie Resende Torres da Silva

Authors
  1. Ana Cláudia de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aeska Lanary Cristino Marques
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lais Leite Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco Xavier de Brito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abrahão Fontes Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marcelo Lourenço da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Josie Resende Torres da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception and design: JRTS, MLS, FXB, AFB. Administrative support: MLS, FXB, AFB. Provision of study materials or patients: ACC, ALCM, LLF, JRTS, FXB. Collection and assembly of data: ACC, ALCM, JRTS, MLS, AFB. Data analysis and interpretation: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors.

Corresponding author

Correspondence to Josie Resende Torres da Silva.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

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.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Medicine.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Carvalho, A.C., Marques, A.L.C., Ferreira, L.L. et al. Transcutaneous Vagus Nerve Stimulation: an Alternative Treatment of Chronic Migraine—a Systematic Review. SN Compr. Clin. Med. 4, 188 (2022). https://doi.org/10.1007/s42399-022-01268-0

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42399-022-01268-0

Keywords

Search

Navigation