Abstract
Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for pain but there is no class 1 study on its role in migraine prophylaxis. In this study we report the efficacy and safety of high-rate rTMS in migraine prophylaxis. Adult migraine patients having >4 attacks/month were randomized to high-rate rTMS or sham stimulation. Stimulation in the form of 10 Hz rTMS, 600 pulses in 10 trains were delivered to the hot spot of the right abductor digiti minimi in 412 s. Three sessions were delivered on alternate days. The outcome was defined at 1 month. The primary outcome measures were reduction in headache frequency and severity >50 % as assessed by the Visual Analogue Scale (VAS). The secondary outcome measures were functional disability, rescue medication and adverse events. Fifty patients each were randomized to rTMS or sham stimulation. The baseline characteristics of rTMS and sham stimulation groups were similar. At 1 month, headache frequency (78.7 vs. 33.3 %; P = 0.0001) and VAS score (76.6 vs. 27.1 %; P = 0.0001) improved significantly in the patients receiving rTMS compared to those in the sham stimulation group. Functional disability also improved significantly in rTMS group (P = 0.0001). Only one patient following rTMS developed transient drowsiness and was withdrawn from the study. This study provides evidence of the efficacy and safety of 10 Hz rTMS in migraine prophylaxis.
Similar content being viewed by others
References
Holland P, Schembri CT, Frederick JP, Goadsby P (2009) Transcranial magnetic stimulation for the treatment of migraine aura? Cephalalgia 29(suppl 1):22 (abstr)
Lipton RB, Pearlman SH (2010) Transcranial magnetic simulation in the treatment of migraine. Neurotherapeutics. 7:204–212
Brighina F, Piazza A, Vitello G, Aloisio A, Palermo A, Daniele O et al (2004) rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study. J Neurol Sci 227:67–71
Teepker M, Hotzel J, Timmesfeld N, Reis J, Mylius V, Haag A et al (2010) Low-frequency rTMS of the vertex in the prophylactic treatment of migraine. Cephalalgia 30:137–144
Mohamad YM, Kothari R, Hughes G et al (2006) Transcranial magnetic stimulation (TMS) relieves migraine headache. Headache 46:839 (abstract)
Mohammad TM, Hughes G, Nkrumah M et al (2006) Self-administered transcranial magnetic stimulation (TMS) during the aura phase improved and aborts headache. Headache 46:857 (abstract)
Clarke BM, Upton AR, Kamath MV, Al-Harbi T, Castellanos CM (2006) Transcranial magnetic stimulation for migraine: clinical effects. J Headache Pain 7:341–346
Lipton RB, Dodick DW, Silberstein SD, Saper JR, Aurora SK, Pearlman SH et al (2010) Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 9:373–380
Conforto A, Goncalves A, Mercante J (2011) Effects of repetitive transcranial magnetic stimulation in chronic migraine: a pilot study. Cephalalgia 31(suppl 1):94
Misra UK, Kalita J, Bhoi SK (2012) High frequency repetitive transcranial magnetic stimulation (rTMS) is effective in migraine prophylaxis: an open labeled study. Neurol Res 34:547–551
Saitoh Y, Yoshimine T (2007) Stimulation of primary motor cortex for intractable deafferentation pain. Acta Neurochir Suppl 97:51–56
Misra UK, Kalita J, Tripathi GM, Bhoi SK (2013) Is β endorphin related to migraine headache and its relief? Cephalalgia 33:316–322
Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders, 2nd edition. Cephalalgia 24:9–160
Piovesan EJ, Silberstein SD (2006) Diagnostic headache criteria and instruments. In: Herndon RM (ed) Handbook of neurologic rating scales, 2nd edn. Demos Medical Publishing, Inc., New York, pp 297–345
Committee Headache Classification, Olesen J, Bousser MG, Diener HC, Dodick D, First M, Goadsby PJ et al (2006) New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 26:742–746
Wong D, Whaley L (1986) Clinical handbook of pediatric nursing, 2nd edn. C.V. Mosby Company, St. Louis
Mathew NT, Saper JR, Silberstein SD, Rankin L, Markley HG, Solomon S et al (1995) Migraine prophylaxis with divalproex. Arch Neurol 52:281–286
Macedo A, Baños JE, Farré M (2008) Placebo response in the prophylaxis of migraine: a meta-analysis. Eur J Pain 12:68–75
Speciali JG, Peres M, Bigal ME (2010) Migraine treatment and placebo effect. Expert Rev Neurother 10(3):413–419
Benedetti F, Mayberg HS, Wager TD, Stohler CS, Zubieta JK (2005) Neurobiological mechanisms of placebo effect. J Neurosci 25:10390–10402
Amanzio M, Benedetti F (1999) Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. J Neurosci 19:484–494
Lefaucheur JP (2006) The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin 36:117–124
Nguyen JP, Nizard J, Keravel Y, Lefaucheur JP (2011) Invasive brain stimulation for the treatment of neuropathic pain. Nat Rev Neurol. 7:699–709
Brighina F, Cosentino G, Vigneri S, Talamanca S, Palermo A, Giglia G et al (2011) Abnormal facilitatory mechanisms in motor cortex of migraine with aura. Eur J Pain 15:928–935
Peyron R, Faillenot I, Mertens P, Laurent B, Garcia-Larrea L (2007) Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study. Neuroimage 34:310–321
Apkarian AV, Bushnell MC, Treede RD, Zubieta JK (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9:463–484
Tracey I (2005) Nociceptive processing in the human brain. Curr Opin Neurobiol 15:478–487
Bestmann S, Baudewig J, Siebner HR, Rothwell JC, Frahm J (2004) Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits. Eur J Neurosci 19:1950–1962
Lefaucheur JP, Antal A, Ahdab R, Ciampi de Andrade D, Fregni F, Khedr EM et al (2008) The use of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to relieve pain. Brain Stimul. 1:337–344
Passard A, Attal N, Benadhira R, Brasseur L, Saba G, Sichere P et al (2007) Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia. Brain. 130:2661–2670
Keck ME, Welt T, Müller MB, Erhardt A, Ohl F, Toschi N et al (2002) Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Neuropharmacology 43:101–109
Strafella AP, Paus T, Barrett J, Dagher A (2001) Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 21:RC157
Michael N, Gosling M, Reutemann M, Kersting A, Heindel W, Arolt V et al (2003) Metabolic changes after repetitive transcranial magnetic stimulation (rTMS) of the left prefrontal cortex. A sham-controlled proton magnetic resonance spectroscopy (1H MRS) study of health brain. Eur J Neurosci 17:2462–2468
May A (2009) New insights into headache: an update on functional and structural imaging findings. Nat Rev Neurol. 5:199–209
Chakravarty A, Mukherjee A, Roy D (2008) Migraine pain location in adult patients from eastern India. Ann Indian Acad Neurol. 11:98–102
Bhoi SK, Kalita J, Misra UK (2012) Metabolic syndrome and insulin resistance in migraine. J Headache Pain. 13:321–326
Acknowledgments
We thank Mr. S. P. Singh for technical assistance and Mr. Rakesh Kumar Nigam for secretarial help.
Conflicts of interest
The authors declare no conflict of interest.
Ethical standard
The research has been approved by the Institutional Ethics Committee, SGPGIMS, Lucknow.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Misra, U.K., Kalita, J. & Bhoi, S.K. High-rate repetitive transcranial magnetic stimulation in migraine prophylaxis: a randomized, placebo-controlled study. J Neurol 260, 2793–2801 (2013). https://doi.org/10.1007/s00415-013-7072-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-013-7072-2