Premonitory phase in primary headaches: shared and divergent mechanisms in migraine and cluster headache, the Junior Editorial Board Members' vision

BACKGROUND AND AIM: Migraine and cluster headache are two highly disabling primary headache disorders, each characterized by distinct clinical phases. Both conditions feature a premonitory phase that precedes the onset of pain or the emergence of cluster bouts, and the symptoms occurring during this stage may provide critical insight into their underlying pathophysiology. This narrative review aims to synthesize current evidence on the premonitory phase of migraine and cluster headache, including its clinical manifestations, neurobiological mechanisms, and potential implications for early or pre-emptive therapeutic strategies. MAIN RESULTS: Migraine patients frequently experience premonitory symptoms before the onset of headache, and multimodal neuroimaging indicates that migraine initiation involves coordinated functional alterations within hypothalamic–brainstem circuits. In cluster headache, premonitory phenomena can be categorized into pre-cluster symptoms, which emerge hours to days before a bout, and pre-attack symptoms, which develop minutes to an hour before an individual attack. Evidence from neuroimaging, genetic, and provocation studies implicates hypothalamic dysfunction, circadian dysregulation, and trigeminal-autonomic network activation as key mechanisms underlying the pre-attack and pre-cluster phases. Across both migraine and cluster headache, early recognition and targeted intervention during the premonitory phase may help prevent or attenuate attacks before the full cascade of nociceptive activation is initiated. CONCLUSIONS: The premonitory phase represents a critical window for understanding the initiation and progression of both migraine and cluster headache. Current evidence suggests that these disorders share partially overlapping neurobiological substrates, particularly involving alterations in hypothalamic function. By elucidating the mechanisms underlying these early phases, future research may help reshape the current clinical paradigm toward truly pre-emptive intervention.