Department of Neurology and Algology, Gazi University Faculty of Medicine, Ankara, Turkey.
Neuroscience and Neurotechnology Center of Excellence (NÖROM), Gazi University, Ankara, Turkey.
J Headache Pain. 2024 Feb 19;25(1):23. doi: 10.1186/s10194-024-01730-5.
Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation.
The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels.
Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores.
We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH.
最近有研究表明，药物过度使用性头痛（MOH）与啮齿动物的肠道渗漏有关。本研究旨在探究偏头痛慢性期（CM）伴 MOH 的患者是否存在循环血中脂多糖（LPS）水平和炎症分子升高的现象。
该研究纳入了女性参与者（40 例 NSAID 过度使用性头痛的 CM 患者、35 例发作性偏头痛（EM）患者和 20 例健康非头痛患者）。记录偏头痛持续时间、每月偏头痛头痛天数、MigSCog、HADS-D、HADS-A 和 HIT-6 评分。采集血清样本以测量循环 LPS、LPS 结合蛋白（LBP）、紧密连接蛋白 occludin、黏附连接蛋白血管内皮钙黏蛋白（VE-cadherin）、CGRP、HMGB1、HIF-1α、IL-6 和 IL-17 水平。
与 EM 组和健康对照组相比，CM+MOH 组的血清 LPS、VE-cadherin、CGRP、HIF-1α 和 IL-6 水平显著升高，而 CM+MOH 组的血清 LBP 和 HMGB1 水平高于健康对照组。三组间 IL-17 和 occludin 水平无差异。与对照组相比，EM 患者的血清 HMGB1 水平升高。与 EM 患者相比，CM+MOH 组的 Mig-SCog 和 HIT-6 评分更高。与 EM 患者和健康对照组相比，CM+MOH 组的 HADS-A 和 HADS-D 评分显著升高，而 EM 患者的 HADS-A 和 HADS-D 评分也高于健康对照组。LPS 水平与 VE-cadherin 和 occludin 水平呈正相关。每月偏头痛头痛天数与血清 LPS、HIF-1α、VE-cadherin 和 IL-6 水平、HADS-A、HADS-D、HIT-6 和 MigSCog 评分呈正相关。
本研究首次证实，CM+MOH 与血清 LPS 和 LBP 水平升高有关，提示 LPS 漏入体循环。HMGB1、HIF-1α、IL-6 和 CGRP 等痛觉和/或促炎分子水平升高可能在 MOH 的三叉神经敏化和神经生物学中发挥作用。肠道通透性增加和随之而来的炎症反应应被视为 MOH 患者的潜在致病因素。
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