{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:26:53Z","timestamp":1787700413200,"version":"build-2784847793"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Migraine is a complex neurological disorder with significant heterogeneity in its clinical presentation and molecular mechanisms. Calcitonin gene-related peptide (CGRP) has emerged as a key player in migraine pathophysiology, but challenges remain in its utilization as a biomarker. This study aimed to investigate salivary CGRP levels during migraine attacks across the frequency spectrum and explore associations with clinical variables.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A prospective longitudinal pilot study was conducted, recruiting migraine patients from an outpatient headache clinic. Salivary CGRP levels were measured at interictal, onset, post-2\u00a0h of onset and end-of-attack. Using generalized linear mixed models, we explored the effect of CGRP changes over the attack in presence of depressive symptoms (DS), acute attack treatment, and after three-months of erenumab treatment. Finally, patients were classified and compared according to their CGRP phenotype.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 44 migraine patients were included (90.9% women), with 80 migraine attacks analyzed. Salivary CGRP levels increased at the onset of migraine attacks. We observed statistically significant interactions between DS and both the linear (Est. [SE]: 19.4 [5.8], <jats:italic>p<\/jats:italic>\u2009=\u20090.001) and quadratic terms of time (-19.1 [6.0], <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Additionally, a significant three-way interaction within the use of acute treated attack (linear-term: -18.5 [6.2], <jats:italic>p<\/jats:italic>\u2009=\u20090.005; quadratic-term: 19.2 [6.8], <jats:italic>p<\/jats:italic>\u2009=\u20090.005) was also found. Molecular phenotyping revealed that 72.7% (32\/44) of patients presented only CGRP-dependent attacks, while 27.3% (12\/44) presented non-CGRP-dependent migraine attacks. Patients with only CGRP-dependent attacks were associated with younger age, shorter disease evolution time, a higher proportion of aura, and fewer monthly headache days (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Exploratory analysis of erenumab treatment effects did not result in changes in CGRP levels during migraine attacks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study underscores the dynamic nature of migraine at a molecular level and emphasizes the importance of integrating clinical variables, such as depressive symptoms, in understanding its pathophysiology. The identification of distinct migraine subtypes based on CGRP dependence suggests potential opportunities for personalized treatment approaches.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-024-01772-9","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T12:01:58Z","timestamp":1713441718000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dynamic fluctuations of salivary CGRP levels during migraine attacks: association with clinical variables and phenotypic characterization"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-9401","authenticated-orcid":false,"given":"Alicia","family":"Alpuente","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3042-2007","authenticated-orcid":false,"given":"Victor J.","family":"Gallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Asskour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5525-0267","authenticated-orcid":false,"given":"Edoardo","family":"Caronna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2856-4134","authenticated-orcid":false,"given":"Marta","family":"Torres-Ferrus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-4702","authenticated-orcid":false,"given":"Patricia","family":"Pozo-Rosich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"1772_CR1","doi-asserted-by":"crossref","unstructured":"Dodick DW (2018) Migraine. 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Curr Opin Neurol 35(3):343\u2013352","journal-title":"Curr Opin Neurol"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-024-01772-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-024-01772-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-024-01772-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T12:02:10Z","timestamp":1713441730000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejournalofheadacheandpain.biomedcentral.com\/articles\/10.1186\/s10194-024-01772-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,18]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1772"],"URL":"https:\/\/doi.org\/10.1186\/s10194-024-01772-9","relation":{},"ISSN":["1129-2377"],"issn-type":[{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,18]]},"assertion":[{"value":"22 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"In relation with this paper the authors have nothing to disclose. AA has received honoraria as speaker from Pfizer, Lundbeck, AbbVie, Novartis and Eli Lilly. VJG has received honoraria as speaker for Eli Lilly and Novartis. LA has nothing to disclose. EC has received honoraria as consultant or speaker for Novartis, Chiesi and Medlink. MT-F has received honoraria as a consultant or speaker for Allergan-Abbvie, Almirall, Chiesi, Eli Lilly, Novartis, Teva and Medlink. In the last five years, PPR has received honoraria as a consultant and speaker for: Abbvie, Amgen, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis and Teva. Her research group has received research grants from AbbVie, Novartis and Teva; and has received funding for clinical trials from Alder, Abbvie, Amgen, Electrocore, Eli Lilly, Lundbeck, Novartis and Teva. She is the Honorary Secretary of the International Headache Society. She is in the editorial board of Neurologia, and Revista de Neurologia, associate editor for Cephalalgia, Headache and The Journal of Headache and Pain. She is a member of the Clinical Trials Guidelines Committee and Scientific Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of . PP-R does not own stocks from any pharmaceutical company.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosure"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}