Mechanistic investigation of HMGB1 in an in vitro model of the trigeminovascular system under migraine-like conditions

Migraine is a complex neurovascular disorder driven by abnormal activation of the trigeminovascular system (TVS), neurogenic inflammation and excessive release of calcitonin gene-related peptide (CGRP). While CGRP-targeted therapies have demonstrated clinical efficacy, the upstream molecular mechanisms sustaining CGRP dysregulation remain incompletely understood. High-mobility group box 1 (HMGB1), a pro-inflammatory damage-associated molecule implicated in neuroinflammation, has emerged as a potential contributor to migraine pathophysiology. However, its role in neuron-endothelial interactions within the TVS under migraine -relevant conditions remains unclear.