Induction of more severe central sensitization in a medication overuse headache model mice through active ingestion of rizatriptan

作者：Zhenjie Ma, Chenhao Li, Wenhao Bai, Wei Xie, Mingjie Zhang, Xiao Han, Cancan Chen, Yang Li, Wenwen Zhang, Deqi Zhai, Yingyuan Liu, Dengfa Zhao, Wenjing Tang, Dong Zhao, Ruozhuo Liu, Shengyuan Yu · 发表于：The Journal of Headache and Pain · 年份：2025 · DOI：10.1186/s10194-025-02066-4 · 被引用次数：11 · 研究领域：Migraine and Headache Studies、Functional Brain Connectivity Studies、Barrier Structure and Function Studies

BACKGROUND: Medication overuse headache (MOH) is a secondary headache disorder arising from excessive use of acute analgesics in patients with primary headache. Current animal models that predominantly employ passive drug administration fail to recapitulate the hallmark feature of voluntary medication-seeking behaviour observed clinically. Therefore, we established a novel MOH mouse model with the active ingestion of rizatriptan (RIZ) to better simulate the clinical characteristics of MOH and explore changes in brain activation patterns. METHODS: C57BL/6 J mice received intraperitoneal injections of nitroglycerin (NTG, 10 mg/kg) every other day. During the feeding period, they were provided with two bottles-one containing an RIZ solution (0.02 mg/kg) and the other containing deuterium depleted water (DDW)-allowing for voluntary intake. The bottle containing the RIZ solution was marked with a fixed colour indicator at the nozzle. Behavioural assessments included mechanical allodynia (von Frey filaments), anxiety-like behaviours (elevated plus maze, EPM and open field test, OFT), and drug-seeking quantification. Quantitative data from c-Fos immunostaining across 25 specific brain regions were subjected to Z score normalization, followed by three-tiered computational analyses: 1) hierarchical clustering (complete linkage) to characterize activation patterns, 2) Pearson correlation analysis for functional connectivity mapping, and 3) graph-theoretical network analysis (Cytoscape ...