Stress as a migraine trigger: clinical evidence and pathophysiological insights. A narrative review

Background: Stress can influence migraine burden and act as a trigger for attacks. However, the relationship between stress and migraine attacks, including its pathophysiological mechanisms, remains unclear. Methods: In this narrative review, we summarized the latest evidence on stress as a potential trigger of migraine attacks and investigated the underlying pathophysiological mechanisms. The literature search was conducted in PubMed, focusing on the time window from 2015 to September 2025. Results: Several studies reported stress as one of the most common migraine triggers. The hypothalamus plays a pivotal role in the stress response and influences its impact on migraine attacks. On one hand, it influences pain perception by modulating pain regions through direct anatomic connections and the release of neuropeptides, such as orexin A and B. On the other hand, through the hypothalamo-pituitary-adrenocortical (HPA) axis, the hypothalamus releases glucocorticoids that can influence cortical excitability and sensitize peripheral structures. Biological sex differences, such as female sex, seem to play an additional and significant role in all these mechanisms. Conclusions: Stress can increase the likelihood of a migraine attack acting as a “catalyst” by influencing cortical excitability and predisposing to nociception. However, other permissive factors must be present to make stress an effective trigger. These include the patient’s state of brain excitability and other biological factors, such as the female sex. Additional and dedicated studies are needed to fully elucidate the relationship between stress and migraine attacks.