title: Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model.
abstract: Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. Here we establish a link between migraine aura and headache by demonstrating that cortical spreading depression, implicated in migraine visual aura, activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Cortical spreading depression caused long-lasting blood-flow enhancement selectively within the middle meningeal artery dependent upon trigeminal and parasympathetic activation, and plasma protein leakage within the dura mater in part by a neurokinin-1-receptor mechanism. Our findings provide a neural mechanism by which extracerebral cephalic blood flow couples to brain events; this mechanism explains vasodilation during headache and links intense neurometabolic brain activity with the transmission of headache pain by the trigeminal nerve.
authors.affiliation: Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hayrunnisa
authors.initials: H
authors.lastname: Bolay
authors.forename: Uwe
authors.initials: U
authors.lastname: Reuter
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Dunn
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Huang
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
authors.forename: Michael A
authors.initials: MA
authors.lastname: Moskowitz
mesh_terms: D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D002421:Caudate Nucleus / Q000502:physiology; D002560:Cerebrovascular Circulation; D013181:Cortical Spreading Depression / Q000502:physiology; D007839:Functional Laterality; D006801:Humans; D008578:Meninges / Q000503:physiopathology*; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology*; D008959:Models, Neurological; D012039:Regional Blood Flow; D018170:Sumatriptan / Q000627:therapeutic use; D014276:Trigeminal Nerve / Q000098:blood supply*
chemical_list: D018170:Sumatriptan