Background : Amygdalin is abundant in Armeniacae semen, and it is recently reported to treat cancers and relieve pain. But modus operandi of amygdalin at the level of neuron has not been reported, yet. Objective : This study aimed to find out the effect of amygdalin on glycine- and glutamate-induced ion currents in periaqueductal gray (PAG) neurons. And it was investigated that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons. Method : We investigated that the changes of glycine- and glutamate-induced ion currents in PAG neurons through application of lipopolysaccharides (LPS) and application of amygdalin with LPS by using the nystatin-perforated patch clamp method. Result : Application of LPS on PAG neurons resulted in increased glycine-induced ion current, and in decreased glutamate-induced ion current. In contrast, application of amygdalin with LPS resulted in decreased glycine-induced ion current increased by LPS, and increased glutamate-induced ion current decreased by LPS. Conclusion : Amygdalin from Armeniacae semen controls glycine- and glutamate-induced ion current by LPS in PAG neurons, and it is suggested that amygdalin participates in the regulation of the descending pain control system in the level of PAG neurons.