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孟鲁司特钠对大鼠缺血再灌注损伤诱导的血管炎性神经痛的改善作用。

Ameliorative potential of montelukast on ischemia-reperfusion injury induced vasculitic neuropathic pain in rat.

机构信息

Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala-147002, Punjab, India.

出版信息

Life Sci. 2012 May 22;90(19-20):755-62. doi: 10.1016/j.lfs.2012.03.010. Epub 2012 Mar 28.

DOI:10.1016/j.lfs.2012.03.010
PMID:22483690
Abstract

AIMS

Ischemia-reperfusion (I/R) event in vascular and nervous system has been documented to rising ischemic and vasculitic neuropathic pain, clinically resembles the complex regional pain syndrome (CRPS). The present study evaluated the effect of montelukast, a cysteinyl leukotriene receptor (Cys-LTC(4) and Cys-LTD(4)) antagonist on ischemia -reperfusion (I/R) induced vasculitic neuropathic pain in rats.

MAIN METHODS

Behavioral parameters were assessed at different time intervals (i.e. 0, 1, 7, 14 and 21st day) and biochemical analysis in sciatic nerve tissue samples were also performed along with histopathological studies.

KEY FINDINGS

Behavioral pain assessment has shown increase in paw and tail withdrawal threshold in montelukast treated groups against thermal and mechanical stimuli as compared to I/R control group. We observed a decrease in the total calcium, thiobarbituric acid reactive substance (TBARS) and myeloperoxidase (MPO) activity levels, whereas there is rise in reduced glutathione level in montelukast treated groups as compared to I/R control group. However, significant behavioral and biochemical results were observed only in medium and high dose of treated groups which were comparable to normal control group. Moreover, histopathological study has revealed the reduction of I/R induced neuronal edema and axonal degeneration due to montelukast.

SIGNIFICANCE

Montelukast has ameliorated I/R induced vasculitic neuropathic pain, these effects may be due to inhibition of lipid peroxidation, reduction of oxidative stress, release of inflammatory mediators and neuroprotective actions. Hence, it could be used as a novel therapeutic agent for the management of vasculitic inflammation related neuropathic pain.

摘要

目的

血管和神经系统的缺血再灌注(I/R)事件已被证明会引起缺血性和血管炎性神经病理性疼痛,临床上类似于复杂性区域疼痛综合征(CRPS)。本研究评估了孟鲁司特(一种半胱氨酰白三烯受体(Cys-LTC(4)和 Cys-LTD(4))拮抗剂)对大鼠缺血再灌注(I/R)引起的血管炎性神经病理性疼痛的影响。

主要方法

在不同时间间隔(即 0、1、7、14 和 21 天)评估行为学参数,并对坐骨神经组织样本进行生化分析,同时进行组织病理学研究。

主要发现

行为学疼痛评估显示,与 I/R 对照组相比,孟鲁司特治疗组在热和机械刺激下的足部和尾部退缩阈值增加。我们观察到总钙、硫代巴比妥酸反应性物质(TBARS)和髓过氧化物酶(MPO)活性水平降低,而孟鲁司特治疗组的还原型谷胱甘肽水平升高。然而,仅在中高剂量治疗组中观察到显著的行为学和生化结果,这些结果与正常对照组相当。此外,组织病理学研究表明,孟鲁司特减少了 I/R 引起的神经元水肿和轴突变性。

意义

孟鲁司特改善了 I/R 引起的血管炎性神经病理性疼痛,这些作用可能是由于抑制脂质过氧化、减少氧化应激、释放炎症介质和神经保护作用。因此,它可以用作治疗血管炎性炎症相关神经病理性疼痛的新型治疗剂。

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