Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats

Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats
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DOI:
10.1016/j.ejpain.2005.08.006
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发表时间:
2006-10-01
影响因子:
3.6
通讯作者:
Kumar, Dinesh
Kumar, Dinesh
中科院分区:
医学2区
文献类型:
--
作者:
Nalk, Ajit K.;Tandan, Surendra K.;Kumar, Dinesh

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目的:本研究的目的是研究活性氧和氧化应激在实验性大鼠坐骨神经慢性压迫性损伤(CCI)的周围神经病变和行为痛反应中的作用。方法:在氯胺酮麻醉的大鼠中,通过右侧坐骨神经CCI诱导神经病理性疼痛,观察N-乙酰-L-半胱氨酸(NAC)腹腔注射对CCI诱导的神经病理性疼痛的影响。还使用伤害性行为测试研究了腹腔内施用NAC在大鼠中的作用。丙二醛,氧化应激和抗氧化酶的指数也估计在结扎坐骨nerve.Results:行为测试,机械,热和冷刺激证实CCI后的神经病理性疼痛的发展结扎坐骨神经的丙二醛水平显着增加相比,非结扎坐骨神经(假手术)。抗氧化酶降低,谷胱甘肽被抑制,而超氧化物歧化酶增加。然而,过氧化氢酶在损伤的坐骨神经中不受影响。NAC腹腔内给药导致显着减少痛觉过敏在CCI诱导的neuropathic rats.Conclusions:本研究确定抗氧化剂超氧化物歧化酶和还原型谷胱甘肽,氧化应激作为重要的决定因素的神经病理和行为后果的CCI诱导的神经病变,和NAC可能是一个潜在的候选人缓解神经病理性疼痛。(C)2005年,国际疼痛研究协会欧洲分会联合会。由爱思唯尔有限公司出版。保留所有权利。
Objectives: The objectives of this study were to examine the role of reactive oxygen species and oxidative stress in peripheral neuropathy and behavioural pain responses in experimentally induced chronic constriction injury (CCI) of sciatic nerve of rat. Effect of N-acetyl-L-Cysteine (NAC) administered intraperitoneally, was also investigated on CCI-induced neuropathic pain in rats.Methods: Neuropathy was induced by CCI of the right sciatic nerve in ketamine anaesthetized rats. Effect of intraperitoneally administered NAC in rats was also investigated using nociceptive behavioural tests. Malondialdehyde, an index of oxidative stress and antioxidant enzymes was also estimated in ligated sciatic nerve.Results: Behavioural tests, mechanical, thermal and cold stimuli confirmed the development of neuropathic pain after the CCI The malondialdehyde levels of ligated sciatic nerves were significantly increased compared to non-ligated sciatic nerves (sham operated). The antioxidant enzyme reduced, glutathione was inhibited, while superoxide dismutase increased. However, catalase remained unaffected in the injured sciatic nerves. Intraperitoneal administration of NAC resulted in significant reduction of hyperalgesia in CCI-induced neuropathic rats.Conclusions: This study identifies antioxidants superoxide dismutase and reduced glutathione, and oxidative stress as important determinants of neuropathological and behavioural consequences of CCI-induced neuropathy, and NAC may be a potential candidate for alleviation of neuropathic pain. (C) 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.