Modulation of Multiple Cranial and Cervical Nerve Sensory Fields for Migraine and Trigeminal Neuropathic Pain
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Mar 6, 2026
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Abstract
The effectiveness of mechanical vibration to sensory fields of cranial nerves CN 5, 7, 8, 9, and 10 and cervical nerves C2 and C3 to mitigate migraine and trigeminal neuropathy pain was assessed. Vibratory devices were fitted within silicon impressions of the auditory meatus in 72 subjects (47 females, 25 males; 15 with trigeminal neuropathy pain, 57 with migraine pain). After initial pain level self-reports, oxygen saturation, heart and respiratory rates, and beat-by-beat blood pressure were collected during a 10-minute control period, followed by 10-minute low- and 20-minute high-amplitude 128 Hz mechanical vibration, and a second 10-minute control period and pain assessment. Migraine and trigeminal pain declined by a mean average of 3.54 (p<0.00001) self-report levels. Visual and vestibular aura were reduced or abolished. Heart rates declined due to vibratory stimulation, and partially recovered post-vibration, but remained lower than at trial onset. In a subset of 20 subjects, successive trials reduced the frequency and intensity of pain attacks over time. Non-invasive mechanical stimulation of cranial and cervical nerves can suppress pain and ameliorate deleterious aura, possibly through action of force sensing Piezo1 and Piezo2 ion channels.
Keywords:
Piezo channels, Vibration, Pain, Heart Rate, Breathing, Neuromodulation, Xerostomia
Article Details
How to Cite
HARPER, Ronald M. et al.
Modulation of Multiple Cranial and Cervical Nerve Sensory Fields for Migraine and Trigeminal Neuropathic Pain.
Medical Research Archives, [S.l.], v. 14, n. 2, mar. 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7186>. Date accessed: 07 mar. 2026.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Unal HA, Basarı A, Celiker OS, Cakar Turhan KS, Asik I, Ozgencil GE. Comparison of Greater Occipital Nerve Blockade and Sphenopalatine Ganglion Blockade in Patients with Episodic Migraine. J Clin Med. 2024 May 21;13(11):3027. doi: 10.3390/jcm13113027.
3. Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs. 2013 Jun;27(6):4 35-55. doi: 10.1007/s40263-013-0063-0.
4. Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005 Feb;25(2):82-6. doi: 10.1111/j.1 468-2982.2005.00611.x.
5. Yuan H, 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.
6. Meng FG, Zhang JG, Schoenen J, Vandersmissen B, Herroelen L, Vandenheede M, Gerard P, Magis D. Migraine prevention with a supraorbital transcutaneous stimulator: a randomized controlled trial. Neurology. 2013 Sep 17;81(12):1102. doi: 0.1212/01.wnl.0000435063.25330.55.
7. Schoenen J, Vandersmissen B, Jeangette S, Herroelen L, Vandenheede M, Gérard P, Magis D. Migraine prevention with a supraorbital transcutaneous stimulator. Neurology 2013;80(8):697-704. doi: 10. 1212/WNL.0b013e3182825055.
8. Reed KL, Black SB, Banta CJ 2nd, Will KR. Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: initial experience. Cephalalgia. 2010 Mar;30(3): 260-71. doi: 10.1111/j.1468-2982.2009.01996.x.
9. Dodick DW, Silberstein SD, Reed KL, Deer TR, Slavin KV, Huh B, Sharan AD, Narouze S, Mogilner AY, Trentman TL, Ordia J, Vaisman J, Goldstein J, Mekhail N. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: long-term results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. 2015 Apr;3 5(4):344-58. doi: 10.1177/0333102414543331.
10. Yarnitsky D, Volokh L, Ironi A, Weller B, Shor M, Shifrin A, Granovsky Y. Nonpainful remote electrical stimulation alleviates episodic migraine pain. Neurology. 2017 Mar 28;88(13):1250-1255. doi: 10.1212/WNL.0000000000003760.
11. Yarnitsky D, Dodick DW, Grosberg BM, Burstein R, Ironi A, Harris D, Lin T, Silberstein SD. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. 2019 Sep;59(8):1240-1252. doi: 10.1111/head.13551.
12. 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. doi: 10.1186/s10194-015-0543-3.
13. Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s4159 8-022-25864-1.
14. 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 Oct;34(12):986-93. doi: 10.1177/0333102414524494.
15. Silberstein SD, Yuan H, Najib U, Ailani J, Morais AL, Mathew PG, Liebler E, Tassorelli C, Diener HC. Non-invasive vagus nerve stimulation for primary headache: A clinical update. Cephalalgia. 2020 Oct;40(12):1370-1384. doi: 10.1177/033310 2420941864.
16. Di Fiore P, Bussone G, Galli A, Didier H, Peccarisi C, D'Amico D, Frediani F. Transcutaneous supraorbital neurostimulation for the prevention of chronic migraine: a prospective, open-label preliminary trial. Neurol Sci. 2017 May;38(Suppl 1):201-206. doi: 10.1007/s10072-017-2916-7.
17. Magis D. Neuromodulation in migraine: state of the art and perspectives. Expert Rev Med Devices. 2015 May;12(3):329-39. doi: 10.1586/174 34440.2015.1005606.
18. Puledda F, Goadsby PJ. An Update on Non-Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine. Headache. 2017 Apr;57(4):685-691. doi: 10.1111/head.13069.
19. Starling AJ, Tepper SJ, Marmura MJ, Shamim EA, Robbins MS, Hindiyeh N, Charles AC, Goadsby PJ, Lipton RB, Silberstein SD, Gelfand AA, Chiacchierini RP, Dodick DW. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 May;38(6):1038-1048. doi: 10.1177/0333102418762525.
20. Lloyd J, Biloshytska M, Andreou AP, Lambru G. Noninvasive Neuromodulation in Headache: An Update. Neurol India. 2021 Mar-Apr;69(12 Suppl 1):S183-S193. doi: 10.4103/0028-3886.315998.
21. Villar-Martinez MD, Goadsby PJ. Non-invasive neuromodulation of the cervical vagus nerve in rare primary headaches. Front Pain Res (Lausanne). 2023 Mar 13;4:1062892. doi: 10.3389/fpain.2023. 1062892.
22. Cocores AN, Smirnoff L, Greco G, Herrera R, Monteith TS. Update on Neuromodulation for Migraine and Other Primary Headache Disorders: Recent Advances and New Indications. Curr Pain Headache Rep. 2025 Feb 15;29(1):47. doi: 10.10 07/s11916-024-01314-7.
23. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010 Oct 1;330(6000):55-60. doi: 10.1126 /science.1193270.
24. Beech DJ, Kalli AC. Force Sensing by Piezo Channels in Cardiovascular Health and Disease. Arterioscler Thromb Vasc Biol. 2019 Nov;39(11): 2228-2239. doi: 10.1161/ATVBAHA.119.313348.
25. Akerman S, Holland PR, Hoffmann J. Pearls and pitfalls in experimental in vivo models of migraine: dural trigeminovascular nociception. Cephalalgia. 2013 Jun;33(8):577-92. doi: 10.1177/ 0333102412472071.
26. Lv X, Wu Z, Li Y. Innervation of the cerebral dura mater. Neuroradiol J. 2014 Jun;27(3):293-8. doi: 10.15274/NRJ-2014-10052.
27. Mosek A, Novak V, Opfer-Gehrking TL, Swanson JW, Low PA. Autonomic dysfunction in migraineurs. Headache. 1999 Feb;39(2):108-17. doi: 10.1046/j.1526-4610.1999.3902108.x.
28. Ebinger F, Kruse M, Just U, Rating D. Cardiorespiratory regulation in migraine. Results in children and adolescents and review of the literature. Cephalalgia. 2006 Mar;26(3):295-309. doi: 10.1111/j.1468-2982.2005.01039.x.
29. Blau JN, Dexter SL. Hyperventilation during migraine attacks. Br Med J. 1980 May 24;280(6226) :1254. doi: 10.1136/bmj.280.6226.1254.
30. Akgün H, Taşdemir S, Ulaş ÜH, Alay S, Çetiz A, Yücel M, Öz O, Odabaşı Z, Demirkaya Ş. Reduced breath holding index in patients with chronic migraine. Acta Neurol Belg. 2015 Sep;115(3):323-7. doi: 10.1007/s13760-014-0375-y.
31. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9-160. doi: 10.1111/ j.1468-2982.2003.00824.x.
32. Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002 Jan;15(1):35-7. doi: 10.1002/ca.1089. PMID: 11835542.
33. Melzack R, Wall PD. Pain mechanisms: a new theory. Science. 1965 Nov 19;150(3699):971-9. doi: 10.1126/science.150.3699.971.
34. Wall PD. The gate control theory of pain mechanisms. A re-examination and re-statement. Brain. 1978 Mar;101(1):1-18. doi: 10.1093/brain/101.1.1.
35. Gesche H, Grosskurth D, Küchler G, Patzak A. Continuous blood pressure measurement by using the pulse transit time: comparison to a cuff-based method. Eur J Appl Physiol. 2012 Jan;112(1):309-15. doi: 10.1007/s00421-011-1983-3.
36. Hennig A. and Patzak A. Continuous blood pressure measurement using pulse transit time. Somnologie 2013, 17(2):104-110. doi: 10.1007/s11 818-013-0617-x
37. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S240-52. doi: 10.1002/acr.20543.
38. Harper, R.M., White, M.R., Harper, R.K., Snodgrass, D., Yan-Go, F. , Jen, J., Taghizadeh, A., Sauerland, E.K.. Sleep induction following cranial nerve modulation in migraine subjects. American Autonomic Society, 28th International Symposium, Clearwater Beach, Florida, 2017.
39. Bigal ME, Serrano D, Reed M, Lipton RB. Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment. Neurology. 2008 Aug 19;71(8):559-66. doi: 10.121 2/01.wnl.0000323925.29520.e7.
40. Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999 Apr 26;159(8):813-8. doi: 10.1001/ archinte.159.8.813.
41. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001 Jul-Aug;41(7):646-57. doi: 10.1046/j.1526-4610.2001.041007646.x.
42. Natoli JL, Manack A, Dean B, Butler Q, Turkel CC, Stovner L, Lipton RB. Global prevalence of chronic migraine: a systematic review. Cephalalgia. 2010 May;30(5):599-609. doi: 10.1111/j.1468-2982 .2009.01941.x.
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