Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats
Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats
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DOI：
10.1097/cad.0000000000000022
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发表时间：
2014-01-01
影响因子：
2.3
通讯作者：
Yamada, Harumi
中科院分区：
文献类型：
--
作者：
Kato, Yoshinori;Tateai, Yoshikazu;Yamada, Harumi
周围神经病变是化疗药物奥沙利铂（Oxp）的常见副作用，并与急性期对冷感觉的超敏反应有关。最近，据报道，日本草药gosha-jinki-gan（GJG）可改善Oxp诱导的冷过敏。然而，这种效应的机制尚未阐明。我们推测GJG对Oxp诱导的冷过敏的作用可能与瞬时受体电位melastatin 8（TRPM 8）和瞬时受体电位锚蛋白1（TRPA 1）通道的表达有关，这是冷门控离子通道。为了评估这一假设，我们研究了GJG和Oxp共同给药后大鼠对冷刺激的戒断反应的改变，以及这种改变的戒断反应与背根神经节（DRG）中TRPM 8和TRPA 1 mRNA表达之间的关系。使用冷板在4 ℃和10 ℃下进行冷超敏反应的评估。与Oxp单独给药相比，GJG（口服剂量：1g/kg/天，持续12天）和Oxp（腹腔注射剂量：4 mg/kg，每周两次）联合给药显著降低了冷刺激的戒断反应。给药第12天，取L4-L 6背根节，RT-PCR法检测TRPM 8和TRPA 1 mRNA的表达。与单独给予Oxp的大鼠相比，联合给予GJG和Oxp的大鼠背根神经节中TRPM 8和TRPA 1的表达显着降低。这些结果表明，GJG的共同管理，可以通过抑制TRPM 8和TRPA 1 mRNA的过表达来改善Oxp诱导的冷过敏。(C)2013年威科健康垂直酒吧利平科特威廉姆斯&威尔金斯。
Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10 degrees C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.