Andoh Tsugunobu, Mizoguchi Shizuka, Kuraishi Yasushi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Tokyo Medical and Dental University, Tokyo, Japan.
J Tradit Complement Med. 2016 Feb 20;7(1):30-33. doi: 10.1016/j.jtcme.2016.01.003. eCollection 2017 Jan.
Oxaliplatin-induced peripheral neuropathy characterized especially as cold dysesthesia is a major dose-limiting side effect of the drug and is very difficult to control. In the present study, we examined whether the traditional herbal formulation Shakuyakukanzoto (SKT: Sháo Yào Gān Cǎo Tāng) could relieve oxaliplatin-induced cold dysesthesia in mice. The inhibitory mechanisms were also investigated. Repetitive administration of SKT (0.1-1.0 g/kg) starting from the day after oxaliplatin injection inhibited cold dysesthesia in a dose-dependent manner. Our previous report has shown that the mRNA expression of transient receptor potential melastatin 8 (TRPM8), characterized as a cold-sensing cation channel, is increased in the dorsal root ganglia of mice treated with oxaliplatin. In addition, TRPM8 antagonist TC-I 2014 (10 and 30 mg/kg) also attenuated cold dysesthesia in oxaliplatin-treated mice. Taken together, it is suggested that TRPM8 is involved in the cold dysesthesia induced by oxaliplatin. Repetitive administration of SKT inhibited the mRNA expression of TRPM8 induced by oxaliplatin in the dorsal root ganglia. These results suggested that prophylactic repetitive administration of SKT is effective in preventing the exacerbation of oxaliplatin-induced cold dysesthesia by inhibiting the mRNA expression of TRPM8 in the dorsal root ganglia.
奥沙利铂诱导的周围神经病变，尤其是以冷感觉异常为特征，是该药物的主要剂量限制性副作用，且很难控制。在本研究中，我们研究了传统草药配方芍药甘草汤（SKT）是否能缓解小鼠奥沙利铂诱导的冷感觉异常。同时也研究了其抑制机制。从奥沙利铂注射后的第二天开始重复给予SKT（0.1 - 1.0 g/kg），以剂量依赖的方式抑制冷感觉异常。我们之前的报告显示，作为一种冷感觉阳离子通道的瞬时受体电位香草酸亚型8（TRPM8）的mRNA表达，在接受奥沙利铂治疗的小鼠背根神经节中增加。此外，TRPM8拮抗剂TC-I 2014（10和30 mg/kg）也减轻了奥沙利铂治疗小鼠的冷感觉异常。综上所述，提示TRPM8参与了奥沙利铂诱导的冷感觉异常。重复给予SKT抑制了奥沙利铂诱导的背根神经节中TRPM8的mRNA表达。这些结果表明，预防性重复给予SKT可通过抑制背根神经节中TRPM8的mRNA表达，有效预防奥沙利铂诱导的冷感觉异常的加重。
