Leaky gut and inflammatory biomarkers in a medication overuse headache model in male rats

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-01 DOI:10.55730/1300-0144.5763

D. Vurallı, Hale Gök Dağıdır, Elif Topa, Hayrunnisa Bolay Belen

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引用次数: 1

Abstract

Background/aim: Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are not completely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is to investigate the role of leaky gut and inflammation in an MOH model MOH model in male rats. Methods: The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronic NSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and the second group was the vehicle group (n = 8) that received 5% dimethyl sulfoxide+sesame oil (ip) for 4 weeks. We assessed spontaneous pain-like behavior, periorbital mechanical withdrawal thresholds, and anxiety-like behavior using an elevated plus maze test. After behavioral testing, serum levels of occludin and lipopolysaccharide-binding protein (LBP) and brain levels of IL-17, IL-6, and high mobility group box 1 protein (HMGB1) were evaluated with ELISA. Results: Serum LBP and occludin levels and brain IL-17 and HMGB1 levels were significantly elevated in the chronic NSAID group compared to its vehicle (p = 0.006, p = 0.016, p = 0.016 and p = 0.016 respectively) while brain IL-6 levels were comparable (p = 0.67) between the groups. The chronic NSAID group showed pain-like and anxiety-like behavior in behavioral tests. Brain IL-17 level was positively correlated with number of head shakes (r = 0.64, p = 0.045), brain IL-6 level was negatively correlated with periorbital mechanical withdrawal thresholds (r = –0.71, p = 0.049), and serum occludin level was positively correlated with grooming duration (r = 0.73, p = 0.032) in chronic NSAID group. Conclusion: Elevated serum occludin and LBP levels and brain IL-17 and HMGB1 levels indicate a possible role of leaky gut and inflammation in an MOH model in male rats. Additionally, a significant correlation between pain behavior and markers of inflammation and intestinal hyperpermeability, supports the role of inflammation and leaky gut in MOH pathophysiology.

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雄性大鼠药物过度使用头痛模型中的肠漏和炎症生物标志物

背景/目的：药物过度使用在慢性偏头痛患者中很常见，而非甾体抗炎药（NSAIDs）是最常被过度使用的药物。过度用药头痛（MOH）的病理生理机制尚未完全明了。据报道，使用非甾体抗炎药的患者会出现肠道高渗透性和肠道渗漏。本研究旨在探讨肠道渗漏和炎症在雄性大鼠 MOH 模型中的作用。研究方法研究对象为雄性 Sprague Dawley 大鼠。分为两个实验组。第一组为慢性非甾体抗炎药组，大鼠腹腔注射甲灭酸 4 周（n = 8）；第二组为载体组（n = 8），大鼠腹腔注射 5%二甲亚砜+芝麻油 4 周（n = 8）。我们使用高架加迷宫试验评估了自发性疼痛样行为、眶周机械退缩阈值和焦虑样行为。行为测试后，我们用酶联免疫吸附法评估了血清中的闭塞素和脂多糖结合蛋白（LBP）水平以及脑中的IL-17、IL-6和高迁移率组盒1蛋白（HMGB1）水平。结果慢性非甾体抗炎药组的血清枸橼酸结合蛋白和闭塞蛋白水平以及脑部IL-17和HMGB1水平与药物组相比明显升高（分别为p = 0.006、p = 0.016、p = 0.016和p = 0.016），而两组间脑部IL-6水平相当（p = 0.67）。慢性非甾体抗炎药组在行为测试中表现出疼痛样和焦虑样行为。慢性非甾体抗炎药组的脑IL-17水平与摇头次数呈正相关（r = 0.64，p = 0.045），脑IL-6水平与眶周机械退缩阈值呈负相关（r = -0.71，p = 0.049），血清闭塞素水平与梳理持续时间呈正相关（r = 0.73，p = 0.032）。结论血清闭塞素和LBP水平的升高以及脑IL-17和HMGB1水平的升高表明，在雄性大鼠的MOH模型中，肠漏和炎症可能起了作用。此外，疼痛行为与炎症标志物和肠道高渗透性之间存在明显的相关性，这支持了炎症和肠道渗漏在 MOH 病理生理学中的作用。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.