{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:25:42Z","timestamp":1786731942801,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["IN607A2022\/07"],"award-info":[{"award-number":["IN607A2022\/07"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013276","name":"Interreg","doi-asserted-by":"publisher","award":["0624_2IQBIONEURO_6_E"],"award-info":[{"award-number":["0624_2IQBIONEURO_6_E"]}],"id":[{"id":"10.13039\/100013276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013276","name":"Interreg","doi-asserted-by":"publisher","award":["EAPA_791\/2018"],"award-info":[{"award-number":["EAPA_791\/2018"]}],"id":[{"id":"10.13039\/100013276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP22\/00061"],"award-info":[{"award-number":["CP22\/00061"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00938"],"award-info":[{"award-number":["PI22\/00938"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015496","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas","doi-asserted-by":"publisher","award":["CB22\/05\/00067"],"award-info":[{"award-number":["CB22\/05\/00067"]}],"id":[{"id":"10.13039\/501100015496","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is the most common neurological disorder and the second most disabling human condition. Autotaxin (ATX) is a plasma enzyme that leads to the formation of lysophosphatidic acid (LPA), which is involved in different functions involved in migraine, such as vascular tone control, inflammation, neuronal excitation, endothelial dysfunction, and neuropathic pain, among others. Most patients with migraine are females and, interestingly, ATX is physiologically higher in the serum of females compared to males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>As ATX may be a link between common mechanisms associated with migraine, we aimed to determine the potential role of ATX in migraine by studying its concentrations in serum between patients with episodic (EM) and chronic migraine (CM) compared to healthy controls, as well as the correlation of ATX with clinical outcomes, and other biomarkers described in migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this cross\u2010sectional study, healthy controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200962), and patients with EM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200945), and CM (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938) were studied. Clinical outcomes, such as migraine intensity as assessed on a visual analog scale (VAS), frequency of headaches (days\/month), evolution time (months), and the duration of attacks (h) were investigated together with the serum biomarkers for inflammation (interleukin 6 [IL\u20106] and IL\u201010), trigeminovascular system activation (calcitonin gene\u2010related peptide [CGRP]), endothelial dysfunction (pentraxin 3 [PTX3], cellular fibrinogen [cFN], soluble tumor necrosis factor\u2010like weak inducer of apoptosis [sTWEAK]), and ATX. Additionally, the serum lipidomic biomarkers profile was also analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum ATX levels were found to be significantly elevated in both patients with EM (mean [standard deviation, SD] 310.7\u2009[79.7]\u2009ng\/mL) and CM (mean [SD] 336.7\u2009[66.9]\u2009ng\/mL) compared to controls (mean [SD] 212.3\u2009[53.2]\u2009ng\/mL) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Elevated ATX levels were associated with migraine outcomes in CM, such as VAS score (Spearman's coefficient\u2009=\u20090.405,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), frequency (Spearman's coefficient\u2009=\u20090.718,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and evolution time (Spearman's coefficient\u2009=\u20090.2257,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). ATX was correlated with CGRP (Pearson's coefficient\u2009=\u20090.278,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), PTX3 (Pearson's coefficient\u2009=\u20090.468,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), sTWEAK (Pearson's coefficient\u2009=\u20090.242,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), cFN (Pearson's coefficient\u2009=\u20090.252,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and IL\u20106 serum levels (Pearson's coefficient\u2009=\u20090.159,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). A drastic decrease in serum lysophosphatidylcholine levels indicates high ATX activity in patients with migraine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Serum levels of ATX were significantly increased in patients with EM and CM. In addition, ATX correlates with clinical outcomes, as well as CGRP, endothelial dysfunction and inflammation biomarkers. Further studies are necessary to elucidate the potential role of ATX as a therapeutic target for migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14922","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:59:37Z","timestamp":1741712377000},"page":"944-960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum levels of autotaxin reveal its role as a novel biomarker of migraine"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-1704","authenticated-orcid":false,"given":"Alberto","family":"Ouro","sequence":"first","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Centro de investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Castro\u2010Mosquera","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00f1a","family":"Rodr\u00edguez\u2010Arrizabalaga","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Debasa\u2010Mouce","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Romaus\u2010Sanjurjo","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Centro de investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Aramburu\u2010Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Centro de investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Iglesias\u2010Rey","sequence":"additional","affiliation":[{"name":"Neuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Casas","sequence":"additional","affiliation":[{"name":"Research Unit on BioActive Molecules, Department of Biological Chemistry Institute for Advanced Chemistry of Catalonia (IQAC\u2010CSIC)  Barcelona Spain"},{"name":"Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Lema","sequence":"additional","affiliation":[{"name":"Corneal Neurodegeneration Group (RENOIR), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Department of Surgery and Medical\u2010Surgical Specialties Faculty of Optics and Optometry, Universidade de Santiago de Compostela  Santiago de Compostela Spain"},{"name":"Instituto Galego de Oftalmolox\u00eda (INGO), Hospital Provincial de Conxo  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Castillo","sequence":"additional","affiliation":[{"name":"Neuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Leira","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Cl\u00ednico Universitario, Universidad de Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Sobrino","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC) Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"},{"name":"Centro de investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01208-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00233"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3057"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22329"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00409-9"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12174"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418774299"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00328-4"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121723"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-234997"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/pmt-2019-0036"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9173090"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102327"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137452"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11071071"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep12548"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002967"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.07.012"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000317R"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.12.041"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83569-3"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040939"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1094705"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04643-8"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20112835"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v5.30741"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030849"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13211"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3988\/jcn.2021.17.2.164"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14088"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0216-y"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01353-0"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2006.00337.x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00367-5"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-017-0536-0"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800055-JLR200"},{"issue":"1","key":"e_1_2_11_39_1","first-page":"33","article-title":"Lipid phosphate phosphatases regulate signal transduction through glycerolipids and sphingolipids. Biochimica et Biophysica Acta (BBA) \u2010 Molecular and Cell Biology of","volume":"1582","author":"Brindley DN","year":"2002","journal-title":"Lipids"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.06.012"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00854.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2020.12.012"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467213999200824124532"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.45560"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01328-1"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168929"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102415607857"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.158642"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.06.007"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2009.02037.x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-007-9579-2"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-013-1542-2"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2005.05135.x"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01377-6"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39797"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20051149"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-018-0665-0"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389-022-00445-z"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00397"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14922","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:43:48Z","timestamp":1762076628000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/head.14922"],"URL":"https:\/\/doi.org\/10.1111\/head.14922","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"2024-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}