Yokukansan (YKS), one of the traditional Japanese “Kampo” medicines, is a mixture of extract powders from seven kinds of medicinal herbs (Atractylodis Lanceae Rhizoma, Hoelen, Cnidii Rhizoma, Uncariae Uncis Cum Ramulus, Angelicae Radix, Bupleuri Radix, and Glycyrrhizae Radix). YKS has been administered to fragile habitus patients who show symptoms such as emotional irritability, neurosis and insomnia, and to infants who suffer from night crying and convulsions. In recent years, YKS has been reported to be effective against pain disorders such as headache and chronic pain, but the mechanism underlying these beneficial effects is still unclear. In this study, the effect of YKS on chronic inflammatory pain and stress caused by pain were investigated using rats with adjuvant arthritis.
Male Wistar rats were injected with complete Freund's adjuvant into the plantar surface of the right hindpaw, and then pain thresholds and stress markers were measured. The thermal pain threshold measured with the plantar test significantly decreased, and the level of salivary chromogranin A (CgA), which is used as a mental stress marker, was significantly increased in this model. The administration of YKS controlled the activation of spinal microglia involved in the expression of chronic pain, and significantly reduced a decrease in the pain threshold. Moreover, an increase in the level of salivary CgA was significantly inhibited. The authors concluded that YKS has effects in reducing chronic inflammatory pain and the stress caused by pain.