The role of opioid receptors in the anti-allodynic effect of local montelukast in a rat chronic constriction injury of sciatic nerve model

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-02-15 DOI:10.1016/j.neulet.2025.138165

Behnam Ghorbanzadeh , Behnam Azizolahi , Mohammad Amin Behmanesh , Parsa Forouhar , Ali Foroughinia , Mohadeseh Nabizadeh

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引用次数: 0

Abstract

Neuropathic pain is a debilitating and chronic condition that results from damage to the peripheral and central nervous system. The inflammatory mediators such as leukotrienes, and opioidergic pathways are involved in the neuropathic pain generation. The present study aimed to determine the effect of local montelukast and the role of opioid receptors using chronic constriction injury (CCI) of the sciatic nerve in rats. Our results showed that montelukast (1–10 mcg/paw) or morphine (1 and 10 mcg/paw) attenuated the mechanical and cold allodynia at day 7 and 14 post-CCI. The effect of montelukast was attenuated by local pre-treatment with naloxone (20 mcg/paw), and was augmented by an ineffective dose of morphine. Also, the histopathological investigation showed the peripheral anti-inflammatory effect of montelukast in the sciatic-injured paw. Moreover, spinal cord mu-opioid receptor mRNA decreased, and kappa-opioid receptor mRNA increased in rats 14 days after CCI by RT-PCR analyses. However, the administration of montelukast on days 7 and 14 after CCI reversed the observed changes in opioid receptors. Our findings suggested that local montelukast can attenuate neuropathic pain, at least in part, through the peripheral opioid receptors, peripheral anti-inflammatory, and also spinal mu- and kappa-opioid receptors. So, local montelukast could be a novel therapeutic strategy for alleviating neuropathic pain.

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阿片受体在孟鲁司特局部抗坐骨神经慢性收缩损伤模型中的作用。

神经性疼痛是一种使人衰弱的慢性疾病，由周围和中枢神经系统的损伤引起。炎症介质如白三烯和阿片能通路参与神经性疼痛的产生。本研究旨在通过大鼠坐骨神经慢性收缩损伤（CCI）来确定局部孟鲁司特的作用和阿片受体的作用。结果显示孟鲁司特（1 ~ 10 mcg/只爪）或吗啡（1 ~ 10 mcg/只爪）在cci后第7天和第14天减轻了机械性和冷性异常性疼痛。孟鲁司特的作用通过纳洛酮（20mcg /paw）局部预处理减弱，通过无效剂量的吗啡增强。同时，组织病理学检查显示孟鲁司特对坐骨损伤足的外周抗炎作用。此外，通过RT-PCR分析，CCI后14 天大鼠脊髓mu-阿片受体mRNA降低，kappa-阿片受体mRNA升高。然而，在CCI后第7天和第14天给予孟鲁司特逆转了观察到的阿片受体的变化。我们的研究结果表明，局部孟鲁司特可以减轻神经性疼痛，至少部分，通过外周阿片受体，外周抗炎，以及脊髓mu-和kappa-阿片受体。因此，局部孟鲁司特可能是缓解神经性疼痛的一种新的治疗策略。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

期刊介绍： Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.