Non-invasive vagus nerve stimulation for primary headache: A clinical update

Author: Stephen D Silberstein1, Hsiangkuo Yuan1, Umer Najib2, Jessica Ailani3, Andreia Lopes de Morais4, Paul G Mathew5 6 7, Eric Liebler8, Cristina Tassorelli9 10, Hans-Christoph Diener11
Author Information:
1 Jefferson Headache Center, Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
2 Department of Neurology, West Virginia University, Morgantown, West Virginia, USA.
3 Medstar Georgetown University Hospital, Washington, DC, USA.
4 Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
5 Harvard Medical School, Boston, Massachusetts, USA.
6 Department of Neurology, Brigham & Women's Hospital, Boston, Massachusetts, USA.
7 Department of Neurology, Harvard Vanguard Medical Associates, Braintree, Massachusetts, USA.
8 electroCore, Inc., Basking Ridge, New Jersey, USA.
9 Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy.
10 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
11 Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty of the University of Duisburg-Essen, Essen, Germany.
Conference/Journal: Cephalalgia
Date published: 2020 Jul 27
Other: Pages: 333102420941864 , Special Notes: doi: 10.1177/0333102420941864. , Word Count: 213

PMID: 32718243 DOI: 10.1177/0333102420941864


Background: Non-invasive vagus nerve stimulation (nVNS) is a proven treatment for cluster headache and migraine. Several possible mechanisms of action by which nVNS mitigates headache have been identified.

Methods: We conducted a narrative review of recent scientific and clinical research into nVNS for headache, including findings from mechanistic studies and their possible relationships to the clinical effects of nVNS.

Results: Findings from animal and human studies have provided possible mechanistic explanations for nVNS efficacy in headache involving four core areas: Autonomic nervous system functions; cortical spreading depression inhibition; neurotransmitter regulation; and nociceptive modulation. We discuss how overlap and interplay among these areas may underlie the utility of nVNS in the context of clinical evidence supporting its safety and efficacy as acute and preventive therapy for both cluster headache and migraine. Possible future nVNS applications are also discussed.

Conclusion: Significant progress over the past several years has yielded valuable mechanistic and clinical evidence that, combined with the excellent safety and tolerability profile of nVNS, suggests that it should be considered a first-line treatment for both acute and preventive treatment of cluster headache, an effective option for acute treatment of migraine, and a highly relevant, practical option for migraine prevention.

Keywords: acute treatment; cluster headache; mechanism of action; migraine; nVNS; preventive treatment.