Prolactin and oxytocin: potential targets for migraine treatment

Abstract

Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development.

Retrospective analysis on the efficacy of epidural labor analgesia on early breast feeding after vaginal delivery

“…However, studies have found that serum prolactin levels have increased in patients with headache, especially migraineand and surgical trauma can activate hypothalamus and pituitary. and cause the increased serum levels of prolactin and oxytocin for regulating nociceptive responses [ 21 , 22 ]. Therefore the pain is a double-edged sword [ 23 ].…”

Molecular and Cellular Neurobiology of Circadian and Circannual Rhythms in Migraine: A Narrative Review

“…Orexins, also known as hypocretins, are neuropeptides synthesized in the lateral hypothalamus [ 79 , 80 , 81 , 82 ]. They are derived from the same precursor, prepro-orexin, and are modified to produce the following two peptides: orexin A (OXA), in a 33-residue peptide, and orexin B (OXB), in a 28-residue peptide [ 80 , 81 ].…”

Considerations for hormonal therapy in migraine patients: a critical review of current practice

“…While the available treatments very often show unsatisfying results, oxytocin and prolactin show potential as therapeutic options in the future. Being currently researched, smaller studies have already indicated that they could have beneficial effects on migraine and, therefore, could represent new targets to tackle the migraine burden [ 152 ]. Exploring future treatment options for migraine is also imperative due to the need to mitigate potential long-term cardiovascular risks associated with CGRP(−receptor) targeted antibodies [ 153 ], and the combined hormonal treatments available [ 87 ].…”