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The aim of this study was to investigate the analgesic effects of analgesic-antitumor peptide (AGAP) and the mechanism of sodium ion channel action by AGAP.A writhing test was applied to investigate the analgesic effects of AGAP,and the whole cell patch clamp technique was used to determine the mechanism of AGAPs effect on sodium channels in primary cultured rat dorsal root ganglion neurons.We found that AGAP inhibited the writhing response in a dose-dependent manner.AGAP (3-1 000 nmol/L) also inhibited INa in a concentration-dependent manner.A 1 000 nmol/L dose of AGAP shifted the sodium channel activation curve to the left.AGAP may reduce the tetrodotoxin-sensitive sodium currents,and significantly shifted the activation curve towards the hyperpolarizing direction and changed its slope.AGAP significantly prolonged the time constant (t) of recovery from inactivation.AGAP at 10-1 000 nmol/L exhibited strong inhibition of tetrodotoxin-resistant Na* currents in small-diameter dorsal root ganglion neurons in a dose-dependent manner.In dorsal root ganglion neurons,the shift in the activation curve was 3.0 mV,and the shift in the inactivation curve was 5.1 mV.Furthermore,the time constant for recovery from inactivation was also extended by 7.6 ms after AGAP administration.These results suggest that AGAP might affect neuronal excitability by interfering with the functioning of sodium channels.The blockage of sodium channels by AGAP may provide a reasonable explanation for the mechanism behind the analgesic effects.