title: Spreading depression triggers headache by activating neuronal Panx1 channels.
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.
authors: Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
authors: Hulya
authors: H
authors: Karatas
authors: Sefik Evren
authors: SE
authors: Erdener
authors: Yasemin
authors: Y
authors: Gursoy-Ozdemir
authors: Sevda
authors: S
authors: Lule
authors: Emine
authors: E
authors: Eren-Koçak
authors: Zümrüt Duygu
authors: ZD
authors: Sen
authors: Turgay
authors: T
authors: Dalkara
mesh_terms: D000344:Afferent Pathways; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology; D020170:Caspase 1 / Q000378:metabolism; D017630:Connexins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013181:Cortical Spreading Depression; D024243:HMGB1 Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008881:Migraine Disorders / Q000378:metabolism / Q000503:physiopathology*; D016328:NF-kappa B / Q000378:metabolism; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D015398:Signal Transduction; D014276:Trigeminal Nerve / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D017630:Connexins; D024243:HMGB1 Protein; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D020170:Caspase 1