P2RX3

P2RX3 (P2X purinoceptor 3), a ligand-gated ion channel activated by extracellular ATP, is predominantly expressed in sensory neurons of trigeminal and dorsal root ganglia. Also termed P2X3, it forms homotrimers or heterotrimers with P2X2 subunits to mediate nociceptive signaling and mechanosensory transduction. Functionally, P2RX3 amplifies pain signals via calcium/sodium influx upon ATP release from damaged cells, engaging pathways like MAPK/ERK and NF-κB to regulate neuronal hyperexcitability. Dysregulation of P2RX3 is implicated in chronic pain syndromes, overactive bladder, and refractory chronic cough, where excessive ATP signaling perpetuates hypersensitivity. Therapeutic antagonists (e.g., gefapixant/AF-219) targeting P2RX3 have advanced to Phase III trials for chronic cough, demonstrating efficacy in reducing cough frequency despite dose-limiting taste disturbances. Emerging candidates like eliapixant (BAY 1817080) show improved selectivity, underscoring P2RX3's potential as a druggable target in neurogenic inflammatory disorders.