Prolactin and oxytocin: potential targets for migraine treatment

Szewczyk AK, Ulutas S, Aktürk T, Al-Hassany L, Börner C, Cernigliaro F, Kodounis M, Lo Cascio S, Mikolajek D, Onan D, Ragaglini C, Ratti S, Rivera-Mancilla E, Tsanoula S, Villino R, Meßlinger K, Maassen Van Den Brink A, de Vries T (2023)

Publication Type: Journal article, Review article

Publication year: 2023

Journal

Journal of Headache and Pain Springer Verlag (Germany) / SpringerOpen

Book Volume: 24

Article Number: 31

Journal Issue: 1

DOI: 10.1186/s10194-023-01557-6

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.

Authors with CRIS profile

Karl Meßlinger Professur für Zelluläre und Molekulare Neurophysiologie

Involved external institutions

Kartal Dr Lutfi Kirdar Training and Research Hospital Dr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi TR Turkey (TR) Erasmus University Medical Center (MC) NL Netherlands (NL) Klinikum der Universität München DE Germany (DE) Università degli Studi di Palermo IT Italy (IT) Eginition Hospital GR Greece (GR) Municipal Hospital Ostrava / Městská Nemocnice Ostrava CZ Czech Republic (CZ) Hacettepe University TR Turkey (TR) University of L'Aquila / Università degli Studi dell'Aquila IT Italy (IT) Medical University of Lublin / Uniwersytet Medyczny w Lublinie PL Poland (PL) 401 General Military Hospital of Athens / 401 Γενικό Στρατιωτικό Νοσοκομείο Αθηνών GR Greece (GR) Universidad de Navarra ES Spain (ES)

How to cite

APA:

Szewczyk, A.K., Ulutas, S., Aktürk, T., Al-Hassany, L., Börner, C., Cernigliaro, F.,... de Vries, T. (2023). Prolactin and oxytocin: potential targets for migraine treatment. Journal of Headache and Pain, 24(1). https://dx.doi.org/10.1186/s10194-023-01557-6

MLA:

Szewczyk, Anna K., et al. "Prolactin and oxytocin: potential targets for migraine treatment." Journal of Headache and Pain 24.1 (2023).

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