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. , ...More

SCIENCE, vol.339, no.6123, pp.1092-1095, 2013 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 339 Issue: 6123
  • Publication Date: 2013
  • Doi Number: 10.1126/science.1231897
  • Journal Name: SCIENCE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1092-1095
  • Hacettepe University Affiliated: Yes

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 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.