Effects of goshajinkigan, hachimijiogan, and rokumigan on mechanical allodynia induced by paclitaxel in mice

Peripheral neuropathy is a major dose-limiting side effect of the chemotherapeutic agent paclitaxel. This study examined whether the three related traditional herbal formulations, goshajinkigan (GJG; Niú Che¯ Shèn Qì Wán), hachimijiogan (HJG; Ba¯ Weì Dì Huáng Wán), and rokumigan (RMG; Liù Weì Wán), would relieve paclitaxel-induced mechanical allodynia in mice. A single intraperitoneal injection of paclitaxel (5 mg/kg) induced mechanical allodynia, which peaked on day 14 after injection. On day 14 after paclitaxel injection, oral administration of GJG (0.1-1.0 g/kg) produced a significant inhibition of established allodynia, but HJG and RMG did not affect the allodynia. Repeated oral administration of GJG (0.1-1.0 g/kg) starting from the day after paclitaxel injection did not affect allodynia development, but significantly inhibited allodynia exacerbation. Repeated oral administration of HJG produced a slight inhibition of allodynia exacerbation, but that of RMG did not. These results suggest that prophylactic administration of GJG is effective in preventing the exacerbation of paclitaxel-induced allodynia. The herbal medicines Plantaginis Semen (Che¯ Qián Z) and Achyranthis Radix (Niú Xi¯), which are present in GJG but not in HJG, may contribute to the inhibitory action of GJG on the exacerbation of paclitaxel-induced allodynia.