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Vagus Nerve Stimulation

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Neuromodulation in Headache and Facial Pain Management

Part of the book series: Headache ((HEAD))

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Abstract

The use of neuromodulatory devices for the treatment of neurological disorders provides a non-invasive and non-pharmacologic therapeutic approach for patients. Recent years have seen a significant increase in the development and assessment of the efficacy of these devices to treat primary headache and facial pain disorders. Non-invasive stimulation of the cervical vagus nerve afferent projection is one such approach whose development is very much advanced, having undergone several clinical trials to assess its efficacy in the treatment of both migraine and cluster headache. There have also been a series of preclinical studies to provide a translational validation of its clinical efficacy, and also as a way to understand the potential mechanism of therapeutic action involved. In this chapter, we will review the anatomy and physiology of the vagus nerve and provide clinical and preclinical evidence to support the medical use of vagus nerve stimulation for the treatment of primary headache and, potentially, facial pains, hypothesising likely mechanism of action.

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References

  1. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005;25(2):82–6. https://doi.org/10.1111/j.1468-2982.2005.00611.x.

    Article  CAS  PubMed  Google Scholar 

  2. Cecchini AP, Mea E, Tullo V, Curone M, Franzini A, Broggi G, et al. Vagus nerve stimulation in drug-resistant daily chronic migraine with depression: preliminary data. Neurol Sci. 2009;30(Suppl 1):S101–4. https://doi.org/10.1007/s10072-009-0073-3.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  4. Sadler RM, Purdy RA, Rahey S. Vagal nerve stimulation aborts migraine in patient with intractable epilepsy. Cephalalgia. 2002;22(6):482–4.

    Article  CAS  PubMed  Google Scholar 

  5. 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. https://doi.org/10.1177/0333102414524494.

    Article  CAS  PubMed  Google Scholar 

  6. 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. https://doi.org/10.1186/s10194-015-0542-4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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. https://doi.org/10.1186/s10194-015-0582-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Nesbitt AD, Marin JC, Tompkins E, Ruttledge MH, Goadsby PJ. Initial use of a novel noninvasive vagus nerve stimulator for cluster headache treatment. Neurology. 2015;84(12):1249–53. https://doi.org/10.1212/WNL.0000000000001394.

    Article  CAS  PubMed  Google Scholar 

  9. Gaul C, Diener HC, Silver N, Magis D, Reuter U, Andersson A, et al. Non-invasive vagus nerve stimulation for PREVention and acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia. 2016;36(6):534–46. https://doi.org/10.1177/0333102415607070.

    Article  PubMed  Google Scholar 

  10. Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317–32. https://doi.org/10.1111/head.12896.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Akerman S, Simon B, Romero-Reyes M. Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache. Neurobiol Dis. 2017;102:96–104. https://doi.org/10.1016/j.nbd.2017.03.004.

    Article  PubMed  Google Scholar 

  12. Chen SP, Ay I, Lopes de Morais A, Qin T, Zheng Y, Sadeghian H, et al. Vagus nerve stimulation inhibits cortical spreading depression. Pain. 2016;157(4):797–805. https://doi.org/10.1097/j.pain.0000000000000437.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Oshinsky ML, Murphy AL, Hekierski H Jr, Cooper M, Simon BJ. Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain. 2014;155(5):1037–42. https://doi.org/10.1016/j.pain.2014.02.009.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Millan MJ. Descending control of pain. Prog Neurobiol. 2002;66(6):355–474.

    Article  CAS  PubMed  Google Scholar 

  15. Ruffoli R, Giorgi FS, Pizzanelli C, Murri L, Paparelli A, Fornai F. The chemical neuroanatomy of vagus nerve stimulation. J Chem Neuroanat. 2011;42(4):288–96. https://doi.org/10.1016/j.jchemneu.2010.12.002.

    Article  CAS  PubMed  Google Scholar 

  16. Kalia M, Sullivan JM. Brainstem projections of sensory and motor components of the vagus nerve in the rat. J Comp Neurol. 1982;211(3):248–65. https://doi.org/10.1002/cne.902110304.

    Article  CAS  PubMed  Google Scholar 

  17. Cheyuo C, Jacob A, Wu R, Zhou M, Coppa GF, Wang P. The parasympathetic nervous system in the quest for stroke therapeutics. J Cereb Blood Flow Metab. 2011;31(5):1187–95. https://doi.org/10.1038/jcbfm.2011.24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Henry TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002;59(6 Suppl 4):S3–14.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. 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. https://doi.org/10.1152/physrev.00034.2015.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 2013;154(Suppl 1):S44–53. https://doi.org/10.1016/j.pain.2013.07.021.

    Article  CAS  PubMed  Google Scholar 

  22. Van Leusden JW, Sellaro R, Colzato LS. Transcutaneous vagal nerve stimulation (tVNS): a new neuromodulation tool in healthy humans? Front Psychol. 2015;6:102. https://doi.org/10.3389/fpsyg.2015.00102.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 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. https://doi.org/10.1515/BMT.2008.022.

    Article  Google Scholar 

  24. Kraus T, Hosl K, Kiess O, Schanze A, Kornhuber J, Forster C. BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J Neural Transm (Vienna). 2007;114(11):1485–93. https://doi.org/10.1007/s00702-007-0755-z.

    Article  CAS  Google Scholar 

  25. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet. 2001;358(9294):1668–75.

    Article  CAS  PubMed  Google Scholar 

  26. Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, et al. Non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a randomised controlled trial (OC-LB-002). Cephalalgia. 2017;37(S1):317–8.

    Google Scholar 

  27. 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. https://doi.org/10.1212/WNL.0000000000002918.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 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. https://doi.org/10.1186/s10194-015-0543-3.

    Article  PubMed  Google Scholar 

  29. Goadsby PJ, de Coo IF, Silver N, Tyagi A, Ahmed F, Gaul C, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. 2018;38(5):959–69. https://doi.org/10.1177/0333102417744362.

    Article  PubMed  Google Scholar 

  30. Simon B, Blake J. Mechanism of action of non-invasive cervical vagus nerve stimulation for the treatment of primary headaches. Am J Manag Care. 2017;23(17 Suppl):S312–S6.

    PubMed  Google Scholar 

  31. Frangos E, Komisaruk BR. Access to vagal projections via cutaneous electrical stimulation of the neck: fMRI evidence in healthy humans. Brain Stimul. 2017;10(1):19–27. https://doi.org/10.1016/j.brs.2016.10.008.

    Article  PubMed  Google Scholar 

  32. Polak T, Markulin F, Ehlis AC, Langer JB, Ringel TM, Fallgatter AJ. Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters. J Neural Transm (Vienna). 2009;116(10):1237–42. https://doi.org/10.1007/s00702-009-0282-1.

    Article  Google Scholar 

  33. Usami K, Kawai K, Sonoo M, Saito N. Scalp-recorded evoked potentials as a marker for afferent nerve impulse in clinical vagus nerve stimulation. Brain Stimul. 2013;6(4):615–23. https://doi.org/10.1016/j.brs.2012.09.007.

    Article  PubMed  Google Scholar 

  34. Nonis R, D’Ostilio K, Schoenen J, Magis D. Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: an electrophysiological study in healthy volunteers. Cephalalgia. 2017;37(13):1285–93. https://doi.org/10.1177/0333102417717470.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Iversen HK, Olesen J. Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs. Cephalalgia. 1996;16(6):412–8.

    Article  CAS  PubMed  Google Scholar 

  36. Iversen HK, Olesen J, Tfelt-hansen P. Intravenous nitroglycerin as an experimental-model of vascular headache - basic characteristics. Pain. 1989;38(1):17–24.

    Article  CAS  PubMed  Google Scholar 

  37. Akerman S, Romero-Reyes M. Targeting the central projection of the dural trigeminovascular system for migraine prophylaxis. J Cereb Blood Flow Metab. 2019;39(4):704–17. https://doi.org/10.1177/0271678X17729280.

    Article  PubMed  Google Scholar 

  38. Akerman S, Holland PR, Summ O, Lasalandra MP, Goadsby PJ. A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization. Brain. 2012;135(Pt 12):3664–75.

    Article  PubMed  Google Scholar 

  39. Robert C, Bourgeais L, Arreto CD, Condes-Lara M, Noseda R, Jay T, et al. Paraventricular hypothalamic regulation of trigeminovascular mechanisms involved in headaches. J Neurosci. 2013;33(20):8827–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ayata C, Lauritzen M. Spreading depression, spreading depolarizations, and the cerebral vasculature. Physiol Rev. 2015;95(3):953–93. https://doi.org/10.1152/physrev.00027.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002;8(2):136–42.

    Article  CAS  PubMed  Google Scholar 

  42. Zhang X, Levy D, Kainz V, Noseda R, Jakubowski M, Burstein R. Activation of central trigeminovascular neurons by cortical spreading depression. Ann Neurol. 2011;69(5):855–65.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rasmussen BK, Olesen J. Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia. 1992;12:221–8.

    Article  CAS  PubMed  Google Scholar 

  44. Akerman S, Goadsby PJ. Topiramate inhibits cortical spreading depression in rat and cat: impact in migraine aura. Neuroreport. 2005;16(12):1383–7.

    Article  CAS  PubMed  Google Scholar 

  45. Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59(4):652–61.

    Article  CAS  PubMed  Google Scholar 

  46. Romero-Reyes M, Akerman S, Nguyen E, Vijjeswarapu A, Hom B, Dong HW, et al. Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse. Headache. 2013;53(1):137–51.

    Article  PubMed  Google Scholar 

  47. Imbe H, Dubner R, Ren K. Masseteric inflammation-induced Fos protein expression in the trigeminal interpolaris/caudalis transition zone: contribution of somatosensory-vagal-adrenal integration. Brain Res. 1999;845(2):165–75.

    Article  CAS  PubMed  Google Scholar 

  48. Yamazaki Y, Ren K, Shimada M, Iwata K. Modulation of paratrigeminal nociceptive neurons following temporomandibular joint inflammation in rats. Exp Neurol. 2008;214(2):209–18. https://doi.org/10.1016/j.expneurol.2008.08.005.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 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(1–2):3–12.

    Article  CAS  PubMed  Google Scholar 

  50. Timarova G, Steno A. Late-onset jaw and teeth pain mimicking trigeminal neuralgia associated with chronic vagal nerve stimulation: case series and review of the literature. BMC Neurol. 2017;17(1):113. https://doi.org/10.1186/s12883-017-0892-4.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Carius A, Schulze-Bonhage A. Trigeminal pain under vagus nerve stimulation. Pain. 2005;118(1–2):271–3. https://doi.org/10.1016/j.pain.2005.07.022.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Neural and Pain Sciences, University of Maryland Baltimore, Baltimore, MD, USA

    Simon Akerman & Marcela Romero-Reyes

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  1. Simon Akerman
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  2. Marcela Romero-Reyes
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Correspondence to Simon Akerman .

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Editors and Affiliations

  1. Headache Centre, Guy’s and St Thomas’, NHS Foundation Trust, Pain Management and Neuromodulation Centre and Neurology Department, London, UK

    Giorgio Lambru

  2. Department de Traitement de la douleur, Centre Hospitalier Universitaire de Nice, Department de Traitement de la douleur, Nice, France

    Michel Lanteri-Minet

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Akerman, S., Romero-Reyes, M. (2020). Vagus Nerve Stimulation. In: Lambru, G., Lanteri-Minet, M. (eds) Neuromodulation in Headache and Facial Pain Management. Headache. Springer, Cham. https://doi.org/10.1007/978-3-030-14121-9_6

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  • DOI: https://doi.org/10.1007/978-3-030-14121-9_6

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