Extracellular ATP and cAMP signaling promote Piezo2‐dependent mechanical allodynia after trigeminal nerve compression injury

• DOI: 10.1111/jnc.15537
• Publication Date: 2021-11-10T16:25:00Z
• Authors: Zhaoke Luo; Xinyue Liao; Lili Luo; Qitong Fan; Xiaofen Zhang; Yuefeng Guo; Feng Wang; Zucheng Ye; Daoshu Luo
• Keywords: Trigeminal ganglion; Cyclic adenosine monophosphate; Mechanotransduction; Apyrase; Nerve Injury; Cyclic guanosine monophosphate; Purinergic Signalling; Dorsal root ganglion; Lingual nerve; Allodynia

Trigeminal neuralgia (TN) is a type of severe paroxysmal neuropathic pain commonly triggered by mild mechanical stimulation in the orofacial area. Piezo2, mechanically gated ion channel that mediates tactile allodynia pain, can be potentiated cyclic adenosine monophosphate (cAMP)-dependent signaling pathway involves exchange protein directly activated cAMP 1 (Epac1). To study whether Piezo2-mediated mechanotransduction contributes to peripheral sensitization rat model TN after trigeminal nerve compression injury, expression Piezo2 and activation signal-related molecules ganglion (TG) were detected. Changes purinergic P2 receptors TG also studied RNA-seq. The cAMP, Epac1 animals increased chronic root (CCT) for 21 days, but knockdown shRNA attenuated allodynia. Purinergic P2X4, P2X7, P2Y1, P2Y2 significantly up-regulated CCT injury. In vitro, neurons was exogenous 5'-triphosphate (ATP) Ca2+ ionophore ionomycin. ATP pre-treated displayed elevated [Ca2+ ]i faster increase responding blockage Na+ /Ca2+ exchanger KB-R7943. Furthermore, cultured led sustained elevation neurons, which much less naïve or reduced inhibitor GsMTx4. These results indicated pivotal role model. Extracellular ATP, influx, cAMP-to-Epac1 synergistically contribute pathogenesis persistence