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Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model

Nature Medicine volume 8, pages 136142 (2002) | Download Citation

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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.

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Acknowledgements

We thank M. Foley for assistance and T. Dalkara for critical review of the manuscript. This study was supported by the NIH Migraine Program Project 2P01 NS10828 (to M.A.M.), NIH 1R29NS38842 (to D.A.B.), NIH K25 NS41291-01 (to A.K.D.), IHS research fellowship and Deutsche Forschungsgemeinschaft Re 1316-1 (to U.R.).

Author information

Author notes

    • Hayrunnisa Bolay
    • , Uwe Reuter
    •  & Andrew K. Dunn

    H.B., U.R. and A.K.D. contributed equally to this study.

Affiliations

  1. Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    • Hayrunnisa Bolay
    • , Uwe Reuter
    • , Zhihong Huang
    •  & Michael A. Moskowitz
  2. NMR Center, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

    • Andrew K. Dunn
    •  & David A. Boas

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The authors declare no competing financial interests.

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Correspondence to Michael A. Moskowitz.

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DOI

https://doi.org/10.1038/nm0202-136

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