Exploring Migraine Pathogenesis: Transcriptomic Insights and Pathway Analysis in Nitroglycerin-Induced Rat Model

Migraine is a chronic neurovascular disease with unclear pathophysiological mechanisms. In this study, its pathogenic mechanisms were investigated through bioinformatics analysis of migraine-related pathways and key genes. Female Sprague Dawley rats were divided into control and migraine model groups. The control group received saline, while the migraine model group received nitroglycerin (NTG) to induce migraines over four weeks. Migraine-like behaviors were assessed within two hours following the final NTG injection. Genes of hypothalamus were identified using DESeq2. Gene ontology enrichment and KEGG pathway analyses were conducted, followed by the identification of hub genes based on protein interaction networks by using algorithms such as Closeness, Degree, and Maximum Neighborhood Component. Rats with NTG-induced migraine showed increased head scratching and cage climbing and a reduced sucrose preference. Transcriptome analysis revealed 1564 differentially expressed genes, with 1233 upregulated and 331 downregulated. Pathways linked to inflammation, PI3K-Akt signaling, and cytokine-cytokine receptor interactions were found to have enriched expression of several genes. Further protein interaction network analysis identified nine hub genes: Alb, Tgfb1, Cd4, Ptprc, Itgb1, Icam1, Col1a1, Pxdn, and Itgad. These findings suggest that migraine involves PI3K-Akt signaling and cytokine-cytokine receptor interactions, providing insights into molecular mechanisms and potential therapeutic targets. However, the study was limited by a small sample size and reliance on a single experimental model, which may constrain the clinical applicability of the findings.