Hypothalamus acts as a central conductor for migraine prodrome symptoms and attack initiation

The migraine prodrome is the earliest phase of a migraine attack, often preceding headache onset by hours or days. Understanding this phase is crucial for elucidating migraine initiation mechanisms and identifying novel targets for acute and preventive treatments. Current standard-of-care often focuses on the headache phase, leaving the prodrome largely unaddressed. The hypothalamus has emerged as a key player due to its involvement in symptoms commonly experienced during prodrome, its influence on critical neuropeptide and neurotransmitter systems, and observed changes in its activity via neuroimaging.

This narrative review systematically summarized evidence implicating the hypothalamus in the migraine prodrome. Researchers conducted a PubMed search on October 29, 2025, using terms such as hypothalamus, prodrome, hypothalamus, premonitory, hypothalamus, migraine, migraine, prodrome, and migraine, premonitory. Full English-language articles were selected based on their relevance to three core areas: symptom localization to the hypothalamus, the hypothalamus's influence on neuropeptide/neurotransmitter production or release, and findings from brain neuroimaging studies.

The review found consistent evidence supporting the hypothalamus's role in migraine prodrome across multiple domains. Migraineurs frequently report prodrome symptoms such as hypersensitivities to visual and auditory stimuli, neck pain, fatigue, sleep-wake disturbances, changes in appetite, mood alterations, and thermoregulation perception issues. Many of these symptoms are directly attributable to the functions of specific hypothalamic subregions and nuclei. > The hypothalamus significantly influences the production or release of several key neuropeptides, neurotransmitters, and hormones implicated in migraine pathophysiology, including calcitonin gene-related peptide (CGRP), dopamine, orexins, and pituitary adenylate cyclase-activating polypeptide (PACAP). Furthermore, brain neuroimaging studies consistently identify changes in hypothalamic activity and functional connectivity during both the prodrome and preheadache phases of a migraine attack, providing objective evidence of its involvement.