Mechanism of NO2-induced migraine in rats: The exploration of the role of miR-653-3p/IGF1 axis

Migraine is a severely disabling primary neurological disorder. Although some studies have confirmed that ni-trogen dioxide (NO2) pollution increases the risk of migraine, and our previous study demonstrated the role of the channel protein transient receptor potential cation channel subfamily V member 1 (TRPV1) in NO2-induced migraine, the underlying mechanisms have not been fully elucidated. This study aimed to explore the intrinsic toxicity mechanism of NO2-induced migraines using transcriptome sequencing. First, the differentially expressed genes in NO2-induced migraine, insulin-like growth factor 1 (IGF1) and miRNA miR-653-3p were identified using RNA and small RNA sequencing, and a protein interaction network was constructed using STRING to explore the possible mechanisms. Next, the targeting relationship between miR-653-3p and IGF1 was determined. NO2- induced migraine was verified by silencing miR-653-3p and IGF1, independently or in combination to regulate the protein kinase B (AKT)/TRPV1 signalling pathway through the miR-653-3p/IGF1 axis. These results indicate that the key molecular mechanism of NO2-induced migraine may be that the miR-653-3p/IGF1 axis regulates the AKT/TRPV1 signalling pathway to induce migraine. The findings of this study will further elucidate the neurotoxic mechanism of NO2-induced migraines and lay a new experimental foundation for implementing migraine-related preventive and therapeutic control measures.