Non-beneficial effects of rosiglitazone in oxaliplatin-induced cold hyperalgesia in rats
Non-beneficial effects of rosiglitazone in oxaliplatin-induced cold hyperalgesia in rats
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DOI：
10.4103/0976-9234.82985
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发表时间：
2011-01-01
影响因子：
--
通讯作者：
Singh, Nirmal
中科院分区：
文献类型：
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作者：
Jain, Vivek;Jaggi, Amteshwar Singh;Singh, Nirmal
背景：研究表明PPAR具有改善的潜力。抗神经损伤性神经病理性疼痛的激动剂。然而，它们在化疗引起的神经病理性疼痛中的作用还没有被探索。目的：研究PPARγ激动剂罗格列酮对奥沙利铂诱导的大鼠冷痛敏的影响。地点和设计：将所有动物分为9组，单次给予奥沙利铂(6 mg/kg)诱导神经病变。材料和方法：采用针刺法、冷浸泡法、热板法和热浸泡法分别评价痛觉过敏、冷痛觉过敏、热痛觉过敏和热刺激痛觉过敏的程度。测定硫代巴比妥酸活性物种(TBARS)和还原型谷胱甘肽(GSH)水平作为氧化应激指标。同时测定髓过氧化物酶(MPO)活性(炎症的特异性标志物)和钙水平。统计分析：行为评价采用双因素方差分析(ANOVA)，行为评价采用Bonferroni后置检验，生化评价采用单因素方差分析(ANOVA)和图基多极差检验。结果：奥沙利铂单次给药后大鼠出现明显的冷痛敏反应，但不改变机械刺激和热刺激的痛觉阈值。此外，奥沙利铂增加了氧化应激，降低了钙水平，但不影响炎症。罗格列酮(2.5、5和10 mg/kg，po)治疗11天不能调节奥沙利铂诱导的冷痛敏。此外，罗格列酮不调节奥沙利铂诱导的生化变化。结论：PPARγ激动剂不能有效减轻奥沙利铂治疗期间的冷痛过敏状态。
Background: Studies have suggested the ameliorative potential of PPAR. agonist in attenuating the nerve injury-induced neuropathic pain. However, their role in chemotherapy-induced neuropathic pain is not explored yet. Aims: To investigate the potential of rosiglitazone, a PPAR gamma agonist, in oxaliplatin-induced cold hyperalgesia in rats. Settings and Design: All animals were divided in nine groups and single administration of oxaliplatin (6 mg/kg ip) used for induction of neuropathy. Material and Methods: The pinprick, cold immersion, hot plate and hot immersion tests were performed to assess the degree of mechanical hyperalgesia, cold hyperalgesia, heat hyperalgesia, and heat allodynia, respectively. The levels of thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) were measured as an index of oxidative stress. The myeloperoxidase (MPO) activity (a specific marker of inflammation) and calcium levels were also determined. Statistical analysis: Two-way analysis of variance (ANOVA) followed by Bonferroni's post test for behavioral assessment and one-way ANOVA followed by Tukey's multiple range tests for biochemical assessment were performed. Results: Single administration of oxaliplatin resulted in significant development of cold hyperalgesia without altering the nociceptive threshold for mechanical and heat stimuli. Furthermore, oxaliplatin increased the oxidative stress and decreased calcium levels without affecting inflammation. Treatment with rosiglitazone (2.5, 5, and 10 mg/kg po) for 11 days did not modulate oxaliplatin-induced cold hyperalgesia. Moreover, rosiglitazone did not modulate oxaliplatin-induced biochemical changes. Conclusions: PPAR gamma agonists are ineffective in attenuating the state of cold hyperalgesia during oxaliplatin administration.