title: Transcranial magnetic stimulation and potential cortical and trigeminothalamic mechanisms in migraine.
abstract: A single pulse of transcranial magnetic stimulation has been shown to be effective for the acute treatment of migraine with and without aura. Here we aimed to investigate the potential mechanisms of action of transcranial magnetic stimulation, using a transcortical approach, in preclinical migraine models. We tested the susceptibility of cortical spreading depression, the experimental correlate of migraine aura, and further evaluated the response of spontaneous and evoked trigeminovascular activity of second order trigemontothalamic and third order thalamocortical neurons in rats. Single pulse transcranial magnetic stimulation significantly inhibited both mechanical and chemically-induced cortical spreading depression when administered immediately post-induction in rats, but not when administered preinduction, and when controlled by a sham stimulation. Additionally transcranial magnetic stimulation significantly inhibited the spontaneous and evoked firing rate of third order thalamocortical projection neurons, but not second order neurons in the trigeminocervical complex, suggesting a potential modulatory effect that may underlie its utility in migraine. In gyrencephalic cat cortices, when administered post-cortical spreading depression, transcranial magnetic stimulation blocked the propagation of cortical spreading depression in two of eight animals. These results are the first to demonstrate that cortical spreading depression can be blocked in vivo using single pulse transcranial magnetic stimulation and further highlight a novel thalamocortical modulatory capacity that may explain the efficacy of magnetic stimulation in the treatment of migraine with and without aura.
authors.affiliation: 1 Department of Neurology, University of California, San Francisco, San Francisco CA, USA 2 Wolfson CARD, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Andreou
authors.affiliation: 3 Headache Group, Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Holland
authors.affiliation: 1 Department of Neurology, University of California, San Francisco, San Francisco CA, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Akerman
authors.affiliation: 1 Department of Neurology, University of California, San Francisco, San Francisco CA, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Summ
authors.affiliation: 4 Neura Inc, Sunnyvale CA, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Fredrick
authors.affiliation: 1 Department of Neurology, University of California, San Francisco, San Francisco CA, USA 3 Headache Group, Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK peter.goadsby@kcl.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
mesh_terms: D000818:Animals; D002415:Cats; D013181:Cortical Spreading Depression / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D017078:Laser-Doppler Flowmetry; D008297:Male; D020325:Migraine with Aura / Q000628:therapy*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000503:physiopathology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D014276:Trigeminal Nerve / Q000503:physiopathology*
keywords: aura; cortical spreading depression; migraine; thalamus; transcranial magnetic stimulation