ObjectiveTo investigate the regulatory effect of protein kinase A (PKA) and protein kinase C (PKC) on the function of ATP receptor P2X3 in cultured dorsal root ganglion (DRG) neurons. MethodsRat DRG neurons were collected, cultured and subjected to exogenous ATP treatment to induce transient inward current. Whole-cell patch clamp recording was employed to observe the effect of TNP-ATP (P2X3 and P2X2/3 receptor antagonist) on the induced current. Meanwhile, the regulatory effects of PKA and PKC agonist on ATP-induced transient inward current were also observed. ResultsTNP-ATP inhibited ATP-induced transient current in cultured DRG neurons in a dose-dependent manner, with the IC50 value being (21.7±7.6) nmol/L. PKA agonist forskolin (1 μmol/L) and PKC agonist PMA (1 μmol/L) inhibited ATP-induced transient current rapidly and reversibly. ConclusionPKA and PKC can inhibit ATP-induced transient inward current in cultured DRG neurons, probably through inhibiting the function of P2X3 receptors. It indicates that P2X3 receptor regulation by protein kinases may participate in the development of pain.