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Neuromodulation in the Management of Headache Disorders
Rashmi Halker MD FAHS

With several invasive and noninvasive devices currently available or in trial, neuromodulation is emerging as a valuable headache treatment option for a variety of reasons. Most notably, the fact that these devices lack the side effects and drug interactions common to medication treatments make them an attractive choice for many individuals. Given the prevalence and disability associated with migraine and cluster headache, much of the research with neuromodulation has centered on these two primary headache disorders.

Single pulse transcranial magnetic stimulation (sTMS) and supraorbital nerve stimulation (SONS) are both noninvasive devices that are available for clinical use and approved for the treatment of migraine. Noninvasive vagus nerve stimulation (nVNS) has shown promise in the management of cluster headache. Given their noninvasive nature, these neuromodulatory tools can be considered as first-line treatment options. Conversely, more invasive neuromodualtion treatments, including occipital nerve stimulation (ONS) and sphenopalatine ganglion (SPG) stimulation, carry more risk and are reserved for refractory patients who have failed other treatments. Taken as a whole, neuromodulation remains an exciting new field with active research from a variety of vantage points, and promises to be a game changer in the way we manage headache disorders.

Neuromodulation reviews

1. D'Andrea, G., D'Arrigo, A., Dalle Carbonare, M. and Leon, A. (2012), Pathogenesis of Migraine: Role of Neuromodulators. Headache: The Journal of Head and Face Pain, 52: 1155–1163. doi:10.1111/j.1526-4610.2012.02168.x
2. Jenkins B and Tepper SJ. Neurostimulation for Primary Headache Disorders, Part 1: Pathophysiology and Anatomy, History of Neuromodulation in Headache Treatment, and Review of Peripheral Neuromodulation in Primary Headaches. Headache: The Journal of Head and Face Pain. 2011;51(8):1254-1256.
3. Jenkins B and Tepper SJ. Neurostimulation for Primary Headache Disorders: Part 2, Review of Central Neurostimulators for Primary Headache, Overall Therapeutic Efficacy, Safety, Cost, Patient Selection, and Future Research in Headache Neuromodulation. Headache: The Journal of Head and Face Pain. 2011;51(9):1408-1418.
4. Robbins MS, Lipton RB. Transcutaneous and Percutaneous Neurostimulation for Headache Disorders. Headache. 2016 Apr 28. doi: 10.1111/head.12829.
5. Láinez, M. J. and Guillamón, E. (2016), Cluster headache and other TACs: Pathophysiology and neurostimulation options. Headache: The Journal of Head and Face Pain. doi:10.1111/head.12874.
6. Shirahige L, Melo L, Nogueira F, Rocha S, Monte-Silva K. Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta-Analysis. Headache. 2016 Nov;56(10):1565-1596. doi: 10.1111/head.12981

Vagus nerve stimulation

1. Yuan H and Silberstein SD. Vagus nerve stimulation and headache. Headache. 2015 Oct 16. doi: 10.1111/head.12721.
2. Yuan H and Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. Headache. 2016 Jan;56(1): 71-8. doi: 10.1111/head.12647.
3. Yuan H and Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II. Headache. 2016 Feb;56(2):259-66. doi: 10.1111/head.12650. Epub 2015 Sep 18.
4. Yuan H and Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III. Headache. 2016 Mar;56(3):479-90. doi: 10.1111/head.12649. Epub 2015 Sep 14.
5. Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, Liebler EJ, Rubenstein Engel E, Tepper SJ. Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study. Headache. 2016 Sep;56(8):1317-32. doi: 10.1111/head.12896.
6. Nonis R, D’Ostilio K, Sava S, Schoenen J, Magis D. Non-invasive Vagus Nerve Stimulation With gammaCore in Healthy Subjects: Is There Electrophysiological Evidence for Activation of Vagal Afferents? Headache. 2016;56:56.

SPG stimulation

1. Yarnitsky D, Goor-Aryeh I, Bajwa ZH, et al. 2003 Wolff Award: Possible parasympathetic contributions to peripheral and central sensitization during migraine. Headache. 2003;43:704-714.
2. Tepper SJ, Rezai A, Narouze S, Steiner C, Mohajer P, Ansarinia M. Acute treatment of intractable migraine with sphenopalatine ganglion electrical stimulation. Headache. 2009 Jul;49(7):983-9. doi: 10.1111/j.1526-4610.2009.01451.x. Epub 2009 May 26.
3. Ansarinia M, Rezai A, Tepper SJ, Steiner CP, Stump J, Stanton-Hicks M, Machado A, Narouze S. Electrical stimulation of sphenopalatine ganglion for acute treatment of cluster headaches. Headache. 2010 Jul;50(7):1164-74. doi: 10.1111/j.1526-4610.2010.01661.x. Epub 2010 Apr 22.
4. Matthew S. Robbins MD, Carrie E. Robertson MD, Eugene Kaplan MD, MPH, Jessica Ailani MD, Larry Charleston IV MD, Deena Kuruvilla MD, Andrew Blumenfeld MD, Randall Berliner MD, Noah L. Rosen MD, Robert Duarte MD, Jaskiran Vidwan DO, Rashmi B. Halker MD, Nicole Gill DO, Avi Ashkenazi MD. The Sphenopalatine Ganglion: Anatomy, Pathophysiology, and Therapeutic Targeting in Headache. Headache. 2016 Feb;56(2):240-58. doi: 10.1111/head.12729. Epub 2015 Nov 30.

Single pulse transcranial magnetic stimulation

1. Siniatchkin M, Kröner-Herwig B, Kocabiyik E, Rothenberger A. Intracortical inhibition and facilitation in migraine--a transcranial magnetic stimulation study. Headache. 2007 Mar;47(3):364-70.
2. Dodick DW, Schembri CT, Helmuth M, Aurora SK. Transcranial magnetic stimulation for migraine: a safety review. Headache. 2010;50:1153-1163.
3. Almaraz AC, Dilli E, Dodick DW. The effect of prophylactic medications on TMS for migraine aura. Headache. 2010 Nov;50(10):1630-3. doi: 10.1111/j.1526-4610.2010.01787.x.
4. Cosentino G, Brighina F, Talamanca S, Paladino P, Vigneri S, Baschi R, Indovino S, Maccora S, Alfonsi E, Fierro B. Reduced threshold for inhibitory homeostatic responses in migraine motor cortex? A tDCS/TMS study. Headache. 2014 Apr;54(4):663-74.
5. Barker AT, Shields K. Transcranial Magnetic Stimulation: Basic Principles and Clinical Applications in Migraine. Headache. 2016 Dec 28. doi: 10.1111/head.13002.

Occipital nerve stimulation

1. Popeney CA, Alo KM. Peripheral neurostimulation for the treatment of chronic, disabling transformed migraine. Headache. 2003;43:369-375.
2. Trentman TL, Zimmerman RS. Occipital nerve stimulation: technical and surgical aspects of implantation. Headache. 2008;48:319-327.
3. Hong J, Ball PA, Fanciullo GJ. Neurostimulation for neck pain and headache. Headache. 2014 Mar;54(3):430-44. doi: 10.1111/head.12292.

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