Abstract: AimTo investigate the effect of capsaicin on I_A and I_K in cultured rat trigeminal ganglion (TG) neurons. MethodsWhole-cell patch clamp technique was used to record the I_A and I_K before and after capsaicin perfusion at different concentrations. ResultsIn capsaicin-sensitive (CS) neurons, capsaicin was shown to selectively inhibit I_A in dose-dependent manner, the IC₅₀ was 0.99 μmol·L^-1. Yet capsaicin showed no inhibitory effect on I_K, capsaicin (10 μmol·L^-1) only slightly inhibited I_K by 13.2%. In capsaicin-insensitive (CIS) neurons, capsaicin (1 μmol·L^-1) showed no significant inhibitory effect on I_A and I_K, capsaicin (10 μmol·L^-1) only slightly inhibited I_A and I_K by 16.8% and 15.3%, respectively. Neither 1 μmol·L^-1 nor 10 μmol·L^-1 capsaicin showed effect on the G-V curve of I_A and I_K. ConclusionCapsaicin was found to selectively inhibit the I_A current in CS neurons, and this effect may contribute to hyperalgesia when capsaicin was first used.