The role of prolactin and oxytocin in migraine pathophysiology

In recent years, researchers have turned their attention to prolactin and oxytocin, exploring how each might contribute differently to the biological processes that drive migraine. Both prolactin and oxytocin rise during lactation; however, they play distinct roles in the perception and regulation of pain. While prolactin is recognized as pronociceptive in migraine, oxytocin exhibits antinociceptive effects. The interactions between prolactin, oxytocin, and calcitonin gene-related peptide (CGRP) receptors are crucial for understanding migraine chronification and susceptibility, especially during periods of hormonal fluctuation. Prolactin and oxytocin exert opposing effects during migraine, enhancing trigeminal nociceptor sensitivity and promoting antinociceptive effects, respectively. Thus, prolactin and CGRP act synergistically to promote trigeminal sensitization, whereas oxytocin counteracts these effects by inhibiting CGRP release. Elevated serum prolactin and oxytocin levels may contribute to migraine pathophysiology through these mechanisms. Overall, the interactions between prolactin and oxytocin levels, their roles in migraine pathophysiology, and their effects on CGRP receptors highlight their potential as therapeutic targets. Therapeutic strategies that reduce prolactin signaling, enhance oxytocin signaling, or directly inhibit CGRP receptors may hold promise for future migraine treatments. Current treatment targets involving prolactin and oxytocin in migraine management remain investigational, and further research is necessary to identify efficacy, optimal dosing, patient selection, and potential sex differences.