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How Migraine Develops

Migraine is a common medical disorder. Unfortunately, how and why migraine headache is initiated is unclear. Karatas et al. (p. 1092) now describe a signaling pathway between stressed neurons and meningeal trigeminal afferents, which may explain how migraine headaches can be generated.

Abstract

The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor κB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed.

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Materials and Methods
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Figs. S1 to S5
Table S1
References (3142)

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References and Notes

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Information & Authors

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Published In

Science
Volume 339 | Issue 6123
1 March 2013

Submission history

Received: 23 October 2012
Accepted: 30 January 2013
Published in print: 1 March 2013

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Acknowledgments

We are grateful to M. A. Moskowitz for helpful discussions, K. Kilic and E. Lule for their expert help with the figures, and to A. Can for his help with confocal microscopy. This work was supported by the Turkish Academy of Sciences (T.D.), Hacettepe University Research Fund 08-D07-101-011 (Y.G.-O.), and the Brain Research Association (H.K.).

Authors

Affiliations

Hulya Karatas
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Sefik Evren Erdener
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Yasemin Gursoy-Ozdemir
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Sevda Lule
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Emine Eren-Koçak
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Zümrüt Duygu Sen
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Psychiatry, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Turgay Dalkara* [email protected]
Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara 06100, Turkey.
Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected]

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