Purpose <p>The pathogenesis of migraine remains incompletely understood, with traditional theories oscillating between purely vascular or strictly neuronal concepts. However, emerging evidence points to a more integrated “vessel-to-neuron” mechanism. This debate paper explores the role of intracranial vasculature in initiating migraine pain, offering a unifying concept that reconciles these traditionally divergent views.</p> Findings <p>Neurosurgical findings confirm that stimulating or mechanically distending intracranial arteries can elicit migraine-like pain, suggesting that these vessels might serve as substrates for migraine pathogenesis. Activation of the trigeminovascular system and subsequent release of migraine-inducing neuropeptides lead to neurogenic inflammation within the meninges, promoting both vasodilation and the sensitization of meningeal nociceptors. Interestingly, all identified molecular migraine triggers potently dilate the intracranial vasculature, converging on potassium efflux from vascular smooth muscle cells. This efflux likely modifies local chemical gradients, thereby depolarizing trigeminal afferents and driving the cascade of ascending nociceptive signaling. Therapeutic interventions further reinforce the causal role of vascular contributions to migraine pathogenesis. Blocking vasodilatory neuropeptides or constricting extracerebral arteries effectively prevents and terminates migraine attacks, underscoring the importance of peripheral mechanisms. More than mere vasodilation, this hypothesis posits that chemical agents, including potassium released by vascular smooth muscle cells, might precipitate migraine onset. The resulting mechano-chemical stimulus might activate perivascular nociceptors and ascending trigeminal pain signaling, ultimately culminating in generation of a migraine attack.</p>