Fig. 4.

Mechanisms of migraine progression. Frequent migaine attacks result in the repetitive and prolonged inflammatory (CGRP-induced) nociception and induce peripheral and then central sensitization. The increase in trigeminal nociceptive sensitivity leads to adaptive changes in several brain networks related to both pain and non-pain behaviours. Chronic medication can alter the endogenous brainstem modulating systems, especially 5-HT dependent and render sensitization process. Combination between increased pain matrix connectivity including hypothalamic hyperactivity and weak 5-HTergic system may contribute to migraine chronification.