Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
Science. 2013 Mar 1;339(6123):1092-5. doi: 10.1126/science.1231897.
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.
偏头痛发展的初始阶段仍知之甚少。在这里，我们描述了皮质扩散性抑制（CSD）期间应激神经元和三叉神经传入之间以前未知的信号通路，CSD 被认为是偏头痛先兆和头痛的原因。CSD 导致神经元 Pannexin1（Panx1）孔道巨孔开放和半胱天冬酶-1 激活，随后神经元高迁移率族蛋白 B1（HMGB1）释放和星形胶质细胞核因子 κB 激活。抑制该级联反应可消除 CSD 诱导的三叉血管激活、脑膜肥大细胞脱颗粒和头痛。CSD 诱导的神经元巨孔开放可能通过到达胶质界膜的实质炎症级联反应促进三叉神经传入的持续激活。该途径可能起到在神经元受到压力时向机体发出头痛警报的作用。
