Abstract
Migraine is a complex neurological disorder with a high disability rate. Although the precipitating factors of migraine remain unclear, previous studies suggest that when there is excess nitrogen dioxide (NO2) pollution in the atmosphere, the medical demand due to migraine attacks increases sharply. However, the main role of NO2 as a trigger for migraine is not yet well understood. The purpose of this study was to explore the relationship between NO2 exposure and the occurrence of migraine as well as the possible underlying mechanisms. We first investigated whether repeated short-term NO2 exposure could induce behavioural and biological migraine phenotypes in rats. Next, capsazepine (CZP) was used to block transient receptor potential cation channel subfamily V member 1 (TRPV1) in vivo, and CZP and vitamin E (VE) were used to verify the role of reactive oxygen species (ROS)-TRPV1 signalling in NO2-induced migraine in primary trigeminal neurones in vitro. We demonstrated that short-term repeated NO2 exposure can significantly induce migraine in rats, and its key molecular mechanism may be related to ROS burst and its downstream TRPV1 channel activation. The findings of this study will enhance the understanding of the neurotoxic mechanism of NO2, provide new clues for identifying the aetiology of migraine, and lay a new experimental basis for implementing migraine-related preventive and therapeutic control measures.