{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:08:44Z","timestamp":1769522924140,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS104200"],"award-info":[{"award-number":["NS104200"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R310\u20102018\u20103711"],"award-info":[{"award-number":["R310\u20102018\u20103711"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex\u2010dependent with variability across a lifetime, indicating the involvement of the hypothalamus\u2010pituitary\u2010gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex\u2010related differences in pain perception.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this systematic review, we searched PubMed and EMBASE for the terms\n                      <jats:italic>prolactin<\/jats:italic>\n                      ,\n                      <jats:italic>hyperprolactinemia<\/jats:italic>\n                      ,\n                      <jats:italic>macroprolactinemia<\/jats:italic>\n                      ,\n                      <jats:italic>hypoprolactinemia<\/jats:italic>\n                      ,\n                      <jats:italic>migraine<\/jats:italic>\n                      ,\n                      <jats:italic>headache<\/jats:italic>\n                      ,\n                      <jats:italic>head pain<\/jats:italic>\n                      , and\n                      <jats:italic>trigeminal pain pathway<\/jats:italic>\n                      to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine\u2010like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene\u2013related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP\u2010induced migraine\u2010like behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo\u2010controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine\u2010attack initiation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14412","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T08:38:45Z","timestamp":1675845525000},"page":"577-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prolactin in headache and migraine: A systematic review of preclinical studies"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1118-9665","authenticated-orcid":false,"given":"Mohammad Al\u2010Mahdi","family":"Al\u2010Karagholi","sequence":"first","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet \u2013 Glostrup, Faculty of Health and Medical Sciences University of Copenhagen  Glostrup 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