Mice with cisplatin and oxaliplatin-induced painful neuropathy develop distinct early responses to thermal stimuli.
Mice with cisplatin and oxaliplatin-induced painful neuropathy develop distinct early responses to thermal stimuli.
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DOI：
10.1186/1744-8069-5-9
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发表时间：
2009-02-26
期刊：
影响因子：
3.3
通讯作者：
Windebank AJ
中科院分区：
文献类型：
--
作者：
Ta LE;Low PA;Windebank AJ
顺铂已经用于治疗生殖细胞和其他形式的癌症已有40年之久。奥沙利铂被批准用于治疗转移性结直肠癌。接受这些药物治疗的癌症患者中有30%到40%会出现疼痛和感觉丧失。奥沙利铂可导致高达80%的患者出现明显的感冒相关感觉障碍。我们已经建立了顺铂和奥沙利铂诱导的神经病变的小鼠模型，使用的剂量与患者使用的剂量相似。成年雄性C57BL6J小鼠每日腹腔注射5天，然后休息5天，共2个周期。总累积剂量顺铂23 mg/kg，奥沙利铂30 mg/kg。行为学评估包括冷盘、von Frey、辐射热、浸尾、握力和探索行为，持续8周。在两个治疗周期后，顺铂和奥沙利铂治疗组的小鼠与对照组小鼠相比表现出显著的机械性痛觉异常。此外，顺铂组大鼠的后爪和尾巴表现出明显的热痛敏反应，奥沙利铂组大鼠的后爪表现出明显的冷过敏反应。因此，我们建立了一个铂类药物诱导的痛性周围神经病变模型，反映了在接受顺铂或奥沙利铂治疗的患者中观察到的早期热痛反应的差异。这个模型在研究这些不同疼痛反应的分子基础和设计保护性治疗策略方面应该是有用的。
Cisplatin has been in use for 40 years for treatment of germ line and other forms of cancer. Oxaliplatin is approved for treatment of metastatic colorectal cancer. Thirty to forty percent of cancer patients receiving these agents develop pain and sensory loss. Oxaliplatin induces distinctive cold-associated dysesthesias in up to 80% of patients. We have established mouse models of cisplatin and oxaliplatin-induced neuropathy using doses similar to those used in patients. Adult male C57BL6J mice were treated with daily intraperitoneal injection for 5 days, followed by 5 days of rest, for two cycles. Total cumulative doses of 23 mg/kg cisplatin and 30 mg/kg oxaliplatin were used. Behavioral evaluations included cold plate, von Frey, radiant heat, tail immersion, grip strength and exploratory behavior at baseline and at weekly intervals for 8 weeks. Following two treatment cycles, mice in the cisplatin and oxaliplatin treatment groups demonstrated significant mechanical allodynia compared to control mice. In addition, the cisplatin group exhibited significant thermal hyperalgesia in hind paws and tail, and the oxaliplatin group developed significant cold hyperalgesia in hind paws. We have therefore established a model of platinum drug-induced painful peripheral neuropathy that reflects the differences in early thermal pain responses that are observed in patients treated with either cisplatin or oxaliplatin. This model should be useful in studying the molecular basis for these different pain responses and in designing protective therapeutic strategies.
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影响因子：
3.4
作者：
Fischer, Stephanie J.;Benson, Linda M.;Windebank, Anthony J.
通讯作者：
Windebank, Anthony J.
影响因子：
5
作者：
Adelsberger, H;Quasthoff, S;Lersch, C
通讯作者：
Lersch, C
DOI：
10.1073/pnas.0504718102
发表时间：
2005-08-09
影响因子：
11.1
作者：
El Maarouf, A;Kolesnikov, Y;Rutishauser, U
通讯作者：
Rutishauser, U
影响因子：
50.5
作者：
Dieras, V;Bougnoux, P;Pouillart, P
通讯作者：
Pouillart, P
影响因子：
2.9
作者：
Cata, Juan P.;Weng, Han-Rong;Dougherty, Patrick M.
通讯作者：
Dougherty, Patrick M.