Spreading Depression Triggers Headache by Activating Neuronal Panx1 Channels
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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Information & Authors
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Published In
Science
Volume 339 | Issue 6123
1 March 2013
1 March 2013
Copyright
Copyright © 2013, American Association for the Advancement of Science.
Submission history
Received: 23 October 2012
Accepted: 30 January 2013
Published in print: 1 March 2013
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.).
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