Dopamine and prolactin in migraine: Mechanisms and potential therapeutic targets

Abstract Migraine is a complex neurovascular disorder characterized by activation and sensitization of the trigeminovascular system. Hyperprolactinemia is associated with headache, and improvement following prolactin‐lowering therapy has been reported in observational studies. Preclinical evidence indicates that prolactin promotes neuronal excitability and sensitization within trigeminal pathways, particularly in females. Downregulation of the protective long prolactin receptor isoform further increases susceptibility to migraine‐relevant triggers. Prolactin secretion is under tonic inhibition by dopamine, a key hypothalamic regulator that also modulates central pain pathways. The role of dopamine in migraine pathophysiology is complex. On one hand, prodromal symptoms such as nausea and yawning are considered dopamine‐mediated. On the other hand, experimental studies show that dopamine directly inhibits nociceptive trigeminovascular activity in addition to lowering prolactin. Dopamine receptor agonists are established treatments for hyperprolactinemia and have demonstrated a positive effect on hyperprolactinemia‐associated headache. A recent placebo‐controlled randomized clinical trial suggests that dopamine agonist treatment can be used as a preventive migraine treatment. In conclusion, prolactin and dopamine may modulate migraine via distinct but converging neuroendocrine pathways, which could represent targets for migraine prevention.