Migraine Chronification Reshapes Brain-Wide Neurovascular Activity During Acute Attacks
Abstract
Abstract Background Migraine attacks represent dynamic transitions between distinct brain states, involving coordinated changes in neuronal activity, trigeminovascular signaling, and cerebrovascular regulation. Although migraine chronification is associated with persistent sensory sensitization and altered brain network organization, whether chronic migraine reshapes the brain-wide neurovascular dynamics underlying acute attacks remains unknown. Nitroglycerin (NTG) is a clinically relevant translational model that reproduces migraine-like attacks and sensitization; however, previous studies have primarily examined regional cortical, meningeal, or large-vessel responses, leaving the temporal organization of whole-brain hemodynamic responses unresolved. In this study, we investigated whether migraine chronification alters the dynamics and network organization of acute attack-related neurovascular responses. Methods A repeated NTG administration paradigm was used to establish a chronic migraine (CM) model, with vehicle-pretreated mice serving as the vehicle (Veh) group. Migraine-related behaviors were evaluated using the mechanical withdrawal threshold, light–dark box testing, and phenol red thread assessment. Separate cohorts underwent continuous whole-brain four-dimensional functional ultrasound (4D fUS) imaging or electroencephalographic (EEG) recordings. Following a 15-min baseline period, an acute NTG challenge was administered, followed by 45 min of continuous recording.…
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