Pregabalin reduces cisplatin-induced mechanical allodynia in rats.
Pregabalin reduces cisplatin-induced mechanical allodynia in rats.
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DOI：
10.1016/j.jphs.2017.06.003
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发表时间：
2017-07
影响因子：
3.5
通讯作者：
Yoshihiro Seto;M. Takase;Y. Tsuji;H. To
中科院分区：
文献类型：
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作者：
Yoshihiro Seto;M. Takase;Y. Tsuji;H. To
顺铂（cisplatin，CDDP）是肿瘤化疗的关键药物，但其引起的周围神经病变是一个剂量限制因素。我们以前报道过，CDDP诱导的周围神经病变，从异常性疼痛发展到痛觉减退，在特定的时间给药CDDP大鼠得到改善。然而，机械性异常性疼痛不能在治疗上预防。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CDDP诱导的大鼠机械性异常性疼痛的影响，雄性Sprague-Dawley大鼠每周5：00静脉注射CDDP（4 mg/kg），连续2周，对照组给予生理盐水。PGN（10 mg/kg/day）每日2次经口给药，时间为8：00和20：00，对照组给予蒸馏水。用von Frey和热板试验评价CDDP引起的周围神经病变，在CDDP引起的机械性异常性疼痛发作前后给予PGN，其戒断阈值均显著高于CDDP单用组。此外，CDDP诱导的机械性异常性疼痛仅被PGN给药所抑制，这些结果表明PGN在给药期间有效地改善了CDDP诱导的机械性异常性疼痛。
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.