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普瑞巴林可减轻顺铂诱导的大鼠机械性异常性疼痛。

Pregabalin reduces cisplatin-induced mechanical allodynia in rats.

作者信息

Seto Yoshihiro, Takase Miyuki, Tsuji Yasuhiro, To Hideto

机构信息

Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama, Japan.

出版信息

J Pharmacol Sci. 2017 Jul;134(3):175-180. doi: 10.1016/j.jphs.2017.06.003. Epub 2017 Jun 20.

Abstract

Although cisplatin (CDDP) is a key drug in cancer chemotherapy, CDDP-induced peripheral neuropathy is a dose-limiting factor. We previously reported that CDDP-induced peripheral neuropathy, which progressed from allodynia to hypoalgesia, was ameliorated by the administration of CDDP to rats at a specific time. However, mechanical allodynia cannot be prevented therapeutically. Pregabalin (PGN) is used to suppress neuropathic pain from herpes zoster and diabetes. Therefore, we investigated the effects of PGN on CDDP-induced mechanical allodynia in rats. CDDP (4 mg/kg) was administered intravenously to male Sprague-Dawley rats at 5:00 once a week for 2 weeks, while saline was given to the control group. PGN (10 mg/kg/day) was administered orally twice a day at 8:00 and 20:00, and distilled water was given to the control group. The von Frey and hot-plate tests were performed to assess CDDP-induced peripheral neuropathy. Withdrawal thresholds were significantly greater than those in with the CDDP alone group when PGN was administered before and after the onset of CDDP-induced mechanical allodynia. Furthermore, CDDP-induced mechanical allodynia was suppressed by the administration of PGN only. These results demonstrate that PGN effectively ameliorates CDDP-induced mechanical allodynia during the administration of PGN.

摘要

尽管顺铂(CDDP)是癌症化疗中的一种关键药物,但顺铂诱导的周围神经病变是一个剂量限制因素。我们之前报道过,顺铂诱导的周围神经病变从痛觉过敏发展为痛觉减退,在特定时间给大鼠施用顺铂可使其得到改善。然而,机械性痛觉过敏无法通过治疗预防。普瑞巴林(PGN)用于抑制带状疱疹和糖尿病引起的神经性疼痛。因此,我们研究了PGN对大鼠顺铂诱导的机械性痛觉过敏的影响。将4毫克/千克的CDDP每周一次于5:00静脉注射给雄性Sprague-Dawley大鼠,持续2周,而对照组给予生理盐水。PGN(10毫克/千克/天)每天8:00和20:00口服给药两次,对照组给予蒸馏水。进行von Frey和热板试验以评估顺铂诱导的周围神经病变。当在顺铂诱导的机械性痛觉过敏发作之前和之后施用PGN时,撤药阈值显著高于单独使用顺铂的组。此外,仅施用PGN就可抑制顺铂诱导的机械性痛觉过敏。这些结果表明,PGN在施用期间可有效改善顺铂诱导的机械性痛觉过敏。

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