OBJECTIVE:To investigate whether the effect of Ioureirin B plus capsaicin on tetrodotoxin-resistant (TTX-R) sodium channel.METHODS:By using whole-cell patch-clamp recordings,in acutely isolated dorsal root ganglion (DRG) neurons,the combined effects of Ioureirin B and capsaicin on TTX-R sodium channel were observed.Based on the data,the interaction between Ioureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed.RESULTS:Loureirin B could not induce transient inward TRPV1 current.Capsazepine,a transient receptor potential vanilloid I (TRPV1) antagonist,could not attenuate the block of 0.64 mmol/L Ioureirin B on TTX-R sodium channel.There was no significant difference (P ＞ 0.05) between IC50 of Ioureirin B (0.37 mmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that (0.38 mmol/L) in capsaicin-insensitive DRG neurons.However,there was a significant difference (P ＜ 0.05) between the IC5o of capsaicin (0.28 μmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that (52.24 μmol/L) in capsaicin-insensitive DRG neurons.Four combinations composed of various concentrations of Ioureirin B and capsaicin could all inhibit TTX-R sodium currents but have different interactions between Ioureirin B and capsaicin.CONCLUSION:Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel.The action of Ioureirin B on TTX-R sodium channel was independent of TRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.