Local preventive effects of shakuyakukanzoto and paeoniflorin external gel on paclitaxel-induced peripheral neuropathic pain in mice

Aim: Chemotherapy for cancer patients induces peripheral neuropathic pain as a refractory side effect. We reported that the prophylactic repeated oral administration of a traditional herbal medicine, shakuyakukanzoto (SKT), peripherally inhibited paclitaxel-induced mechanical allodynia in mice. In the present study, we therefore developed external gel forms of SKT and the major constituent paeoniflorin (PF), and evaluated their effects on paclitaxel-induced mechanical allodynia in mice. Methods: A single intraperitoneal injection of paclitaxel was given to mice. SKT or PF external gel (SKT-Gel or PF-Gel) was topically applied to the right planar surface twice daily for 13 days. Mechanical allodynia was evaluated by the von Frey filament test. Results: The prophylactic repeated topical application of SKT-Gel or PF-Gel on the right planar surface inhibited the exacerbation of paclitaxel-induced mechanical allodynia. However, the prophylactic repeated topical application of external base gel (BS-Gel) on the left planar surface in the same mice treated with paclitaxel did not affect the allodynia. Conclusion: Prophylactic repeated topical applications of SKT-Gel and PF-Gel locally inhibited the exacerbation of paclitaxel-induced mechanical allodynia. These gels were useful for the control of paclitaxel-induced peripheral neuropathic pain.