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Both affect pain processing and stress response by interfering with neural and brain hypersensitivity and by interacting with chemokines and cytokines that control vascular and inflammatory processes. The involvement of these pathways in migraine has been widely studied, but acute citalopram neuroendocrine challenge on TRP metabolism and cytokine profile has not been investigated yet. In our study, females with episodic migraine without aura and healthy controls were studied before and after acute citalopram or placebo in a double-blind setting. At baseline, increased TRP\/large neutral amino acid (LNAA) ratio and decreased RANTES chemokine concentration were detected in migraine patients compared to controls. The challenge induced a significant increase in TRP, KYN, and TRP\/LNAA in healthy controls, but not in migraine patients. Furthermore, migraine attack frequency negatively correlated with KYN\/TRP ratio and positively correlated with the neuroendocrine-challenge-induced KYN concentration increase. Our results support a decreased breakdown of TRP via KYN pathway and a failure to modulate TRP\u2013KYN pathway during citalopram-induced acute stress together with an increased vascular sensitivity in migraine. These mechanisms may provide useful drug targets for future drug development.<\/jats:p>","DOI":"10.3390\/cells11142258","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T10:36:56Z","timestamp":1658399816000},"page":"2258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Citalopram Neuroendocrine Challenge Shows Altered Tryptophan and Kynurenine Metabolism in Migraine"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-2572","authenticated-orcid":false,"given":"Kinga","family":"Gecse","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, Hungary"},{"name":"SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, 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Informatics, Budapest University of Technology and Economics, Magyar Tud\u00f3sok krt.2, H-1521 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"Demeter","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, Hungary"},{"name":"SE-NAP2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8411-0773","authenticated-orcid":false,"given":"D\u00e1vid","family":"Vir\u00e1g","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, 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Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"K\u00f6rnyei","sequence":"additional","affiliation":[{"name":"Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Szigony Street 43, H-1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Denes","sequence":"additional","affiliation":[{"name":"Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Szigony Street 43, H-1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Bagdy","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, Hungary"},{"name":"NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, \u00dcll\u0151i Street 26, H-1085 Budapest, Hungary"},{"name":"MTA-SE 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