Fig. 4

A single CSD or synaptic stress induces the opening of neuronal Panx1 channels, formation of the inflammasome complex, activation of caspase-1, and subsequent release of IL-1β and HMGB1, which induce translocation of NF-ĸB pairs to the nucleus to initiate pro-inflammatory transcription in astrocytes. The pro-inflammatory transcription in astrocytes leads to the induction of enzymes such as COX2 and iNOS or cytokines such as CCL2. The subsequent release of prostaglandins, NO, and cytokines from the astrocyte endfeet along the glia limitans can activate/sensitize the pial nociceptors, thereby contributing to sustaining headache. ATP release from Panx1 channels attracts microglia processes that continuously survey the spines via P2Y12 receptors to repair injured spines. Illustrations were created using Servier Medical Art (http://www.servier.com)