钾离子通道在奥沙利铂诱导的周围神经痛中的作用

Effect of potassium channel on oxaliplatin-induced neuropathic pain

目的:探讨奥沙利铂诱导的神经病理性疼痛的作用机制。方法:SD大鼠腹腔注射奥沙利铂,剂量为4.8mg/kg,注射时间为第1、2、8、9、15、16、22天,共7次。应用Von-Frey丝、热痛仪、冷板试验测量大鼠的行为学变化。灌胃给予氟吡汀,检测模型动物的行为学变化。给药3、8、15d后,取SD大鼠第4~5腰椎(L4~L5)背根神经节(DRG),检测DRG中Kv1.2mRNA和蛋白的表达变化及分布情况。结果:腹腔注射奥沙利铂后大鼠的机械阈值、冷觉阈值均降低,阈值变化均具有统计学意义,热痛阈值和体质量无变化。通过灌胃给予氟吡汀后大鼠机械阈值和冷觉阈值均回升,与奥沙利铂对照组相比,差异有统计学意义。奥沙利铂组大鼠3、8、15d的DRG神经元中Kv1.2mRNA和蛋白的表达均减低。免疫组织化学显色显示Kv1.2可以与CGRP、NF-200、IB4分别共标,与GS不共标。结论:奥沙利铂诱导的周围神经病理性疼痛的产生和发展可能与钾离子通道变化有关,给予钾离子通道的兴奋剂氟吡汀可以缓解其疼痛。

Objective:To investigate the mechanism of oxaliplatin-induced neuropathic pain.Methods:SD male rats were intraperitoneally administered with 4.8mg/kg of oxaliplatin at day 1,2,8,9,15,16,22.Behaviors were measured by von-Frey filament,cold plate and thermal test apparatus.Intragastric administration of flupirtine and to detect the behavior changes of model rats.Dorsal root ganglion(DRG)of L4-L5 were achieved at 3,8,15d post oxaliplatin administration.q-PCR and Western blotting were applied to detect the expression of mRNA and protein of Kv1.2 in DRG.Immunofluorescence was used to detect distribution of the Kv1.2 in DRG.Results:Oxaliplatin administration for seven times caused significant mechanical and cold allodynia that appeared 8 days after the first injection,however,thermal allodynia and weight were not changed.The mechanical threshold and cold threshold of rats in Oxaliplatin group were reversed by intragastric administration of flupirtine.The expression of mRNA and protein of Kv1.2 were decreased in Oxaliplatin group.The Kv1.2 was co-expressed with CGRP,NF-200,and IB4,while it was not found to localize with GS.Conclusion:Potassium channels may be involved in oxaliplatin-induced neuropathic pain and flupirtine can relieve the pain.