Spreading Depression Triggers Headache by Activating Neuronal Panx1 Channels

KARATAS H. , ERDENER Ş. E. , GURSOY-OZDEMIR Y., Lule S. , EREN-KOCAK E. , Sen Z. D. , ...Daha Fazla

SCIENCE, cilt.339, sa.6123, ss.1092-1095, 2013 (SCI İndekslerine Giren Dergi) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 339 Konu: 6123
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1126/science.1231897
  • Dergi Adı: SCIENCE
  • Sayfa Sayıları: ss.1092-1095


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 kappa B 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.