Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model.
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.
Bolay
Hayrunnisa
H
Stroke and Neurovascular Regulation Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Reuter
Uwe
U
Dunn
Andrew K
AK
Huang
Zhihong
Z
Boas
David A
DA
Moskowitz
Michael A
MA
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*
D018170:Sumatriptan