Ginseng total saponin potentiates acute U-50,488H-induced analgesia and inhibits tolerance to U-50,488H-induced analgesia in mice

Abstract

In the present study, an attempt has been made to investigate whether the potentiating effect of U-50,488H (U50)-induced analgesia by ginseng total saponin (GTS) is playing a role in inhibiting the tolerance to U50-induced analgesia as measured using the tail-flick test in mice. GTS (100 and 200 mg/kg ip), on acute administration, potentiated the U50 (40 mg/kg ip)-induced analgesia in U50-naive mice. Twice daily administration of U50 (40 mg/kg ip) for 6 days resulted in tolerance to U50-induced analgesia in mice. Chronic administration (Days 4–6) of GTS (50, 100, and 200 mg/kg ip) to U50-tolerant mice dose-dependently inhibited the tolerance to U50-induced analgesia. On the other hand, chronic administration of GTS (50, 100, and 200 mg/kg ip) dose-dependently potentiated the U50-induced analgesia in U50-naive mice. The dose–response curve to U50-induced analgesia in U50-tolerant mice was shifted rightward (2.6-fold) as compared to U50-naive mice, indicating the development of tolerance to U50-induced analgesia. GTS (100 mg/kg ip od), on chronic administration, prevented the rightward shift of dose–response curve to U50-induced analgesia in U50-tolerant mice, whereas in U50-naive mice it resulted in leftward shift (0.6-fold). It can be concluded that acute and chronic administration of GTS potentiates the U50-induced analgesia in U50-naive mice. The potentiating effect of GTS on U50-induced analgesia may be partially responsible in the inhibition of tolerance to U50-induced analgesia in mice.