Fig. 3

Neuronal Panx1 channel opening after CSD initiates a neuroinflammatory cascade, characterized by inflammasome formation and caspase-1 activation in neurons followed by release of HMGB1 and IL-1β, which trigger NF-κB nuclear translocation in astrocytes. A, B NF-κB leads to pro-inflammatory transcriptional activity and secretion of nitric oxide, cytokines and prostanoids from astrocyte endfeet, reaching meningeal nociceptors by way of meningo-astroglial network (C) to stimulate them (from [2 and 100], with permission). In A, red labels show agents used to inhibit each step in the inflammatory cascade and red circles represent propidium iodide (PI) influx through open Panx1 channels