Ameliorative potential of pioglitazone and ceftriaxone alone and in combination in rat model of neuropathic pain: Targeting PPARγ and GLT-1 pathways
Ameliorative potential of pioglitazone and ceftriaxone alone and in combination in rat model of neuropathic pain: Targeting PPARγ and GLT-1 pathways
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DOI：
10.1016/j.pharep.2015.06.010
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发表时间：
2016-01-01
影响因子：
4.4
通讯作者：
Ekavali, E.
中科院分区：
文献类型：
--
作者：
Pottabathini, Raghavender;Kumar, Anil;Ekavali, E.
背景：谷氨酸稳态与 PPAR γ 之间的关系在神经创伤和疼痛中具有极其重要的意义。本研究旨在阐明GLT-1激活剂（头孢曲松）和PPARγ激动剂（吡格列酮）在脊神经结扎引起的神经性疼痛中的相互作用。方法：对雄性SD大鼠进行脊神经结扎以诱导神经性疼痛。吡格列酮、头孢曲松及其联合治疗持续28天。随后评估了各种行为、生化、神经炎症和细胞凋亡介质。结果：在本研究中，L5和L6脊神经的结扎导致对不同机械和热刺激的明显痛觉过敏和异常性疼痛。此外，脊髓神经结扎大鼠的脊髓中氧化亚硝化应激参数、炎症和细胞凋亡标记物显着增加。吡格列酮和头孢曲松治疗显着阻止了大鼠的这些行为、生化、线粒体和细胞改变。此外，吡格列酮（10 mg/kg，腹膜内）与头孢曲松（100 mg/kg，腹膜内）的组合与其本身的作用相比显着增强了保护作用。结论：基于这些结果，我们提出吡格列酮和头孢曲松的神经保护作用之间可能存在相互作用，抑制行为、生化、线粒体、 脊髓神经结扎中的神经炎症和细胞凋亡级联引起大鼠神经性疼痛。 (c) 2015 年波兰科学院药理学研究所。由爱思唯尔公司出版。 z o.o.版权所有。
Background: The relation between glutamate homeostasis and PPAR gamma has got tremendous importance in nerve trauma and pain. Present study has been designed to elucidate the interaction between the GLT-1 activator (ceftriaxone) and PPAR gamma agonist (pioglitazone) in the spinal nerve ligation induced neuropathic pain.Methods: Male SD rats were subjected to spinal nerve ligation to induce neuropathic pain. Pioglitazone, ceftriaxone and their combination treatments were given for 28 days. Various behavioral, biochemical, neuroinflammatory and apoptotic mediators were assessed subsequently.Results: In the present study, ligation of L5 and L6 spinal nerves resulted in marked hyperalgesia and allodynia to different mechanical and thermal stimuli. In addition there is marked increase in oxidative-nitrosative stress parameters, inflammatory and apoptotic markers in spinal cord of spinal nerve ligated rats. Treatment with pioglitazone and ceftriaxone significantly prevented these behavioral, biochemical, mitochondrial and cellular alterations in rats. Further, combination of pioglitazone (10 mg/kg, ip) with ceftriaxone (100 mg/kg, ip) significantly potentiated the protective effects as compared to their effects per se.Conclusion: Based on these results we propose that possible interplay between the neuroprotective effects of pioglitazone and ceftriaxone exists in suppressing the behavioral, biochemical, mitochondrial, neuroinflammatory and apoptotic cascades in spinal nerve ligation induced neuropathic pain in rats. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.