Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model

Nat Med. 2002 Feb;8(2):136-42. doi: 10.1038/nm0202-136.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brain / blood supply
  • Brain / physiopathology*
  • Caudate Nucleus / physiology
  • Cerebrovascular Circulation
  • Cortical Spreading Depression / physiology
  • Functional Laterality
  • Humans
  • Meninges / physiopathology*
  • Migraine Disorders / drug therapy
  • Migraine Disorders / physiopathology*
  • Models, Neurological
  • Regional Blood Flow
  • Sumatriptan / therapeutic use
  • Trigeminal Nerve / blood supply*


  • Sumatriptan