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The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide. Its activity has been associated with several molecular processes involved in migraine. Therefore, this cross-sectional study aims to study the potential role of aSMase in patients with episodic and chronic migraine. In this cross-sectional pilot study, serum samples from female healthy controls (n = 23), episodic migraine (EM) patients (n = 31), and chronic migraine (CM) patients (n = 28) were studied. The total serum levels of aSMase were determined by ELISA. In addition, the serum levels of sphingomyelin (SM), dihydro-sphingomyelin (dhSM), ceramide (Cer), and dihydro-ceramide (dhCer) were determined by mass spectrometry as biomarkers involved in the main molecular pathways associated with aSMase. aSMase serum levels were found significantly elevated in both EM (3.62 \u00b1 1.25 ng\/mL) and CM (3.07 \u00b1 0.95 ng\/mL) compared with controls (1.58 \u00b1 0.72 ng\/mL) (p &lt; 0.0001). ROC analysis showed an area under the curve (AUC) of 0.94 (95% CI: 0.89\u20130.99, p &lt; 0.0001) and 0.90 (95% CI: 0.81\u20130.99, p &lt; 0.0001) for EM and CM compared to controls, respectively. Regarding other biomarkers associated with aSMase\u2019s pathways, total SM serum levels were significantly decreased in both EM (173,534 \u00b1 39,096 pmol\/mL, p &lt; 0.01) and CM (158,459 \u00b1 40,010 pmol\/mL, p &lt; 0.0001) compared to the control subjects (219,721 \u00b1 36,950 pmol\/mL). Elevated serum levels of aSMase were found in EM and CM patients compared to the control subjects. The decreased SM levels found in both EM and CM indicate that aSMase activity plays a role in migraine. Therefore, aSMase may constitute a new therapeutic target in migraine that should be further investigated.<\/jats:p>","DOI":"10.3390\/antiox14020159","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T04:36:18Z","timestamp":1738125378000},"page":"159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine"],"prefix":"10.3390","volume":"14","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), 15706 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3590-002X","authenticated-orcid":false,"given":"M\u00f3nica","family":"Castro-Mosquera","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-8037","authenticated-orcid":false,"given":"Mari\u00f1a","family":"Rodr\u00edguez-Arrizabalaga","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9511-7399","authenticated-orcid":false,"given":"Manuel","family":"Debasa-Mouce","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1122-0351","authenticated-orcid":false,"given":"Ant\u00eda","family":"Custodia","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1212-9851","authenticated-orcid":false,"given":"Marta","family":"Aramburu-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7715-1956","authenticated-orcid":false,"given":"Daniel","family":"Romaus-Sanjurjo","sequence":"additional","affiliation":[{"name":"NeuroAging Group Laboratory (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7926-5209","authenticated-orcid":false,"given":"Josefina","family":"Casas","sequence":"additional","affiliation":[{"name":"Research Unit on BioActive Molecules, Department of Biological Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), 08034 Barcelona, Spain"},{"name":"Liver and Digestive Diseases Networking Biomedical Research Centre (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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), 15706 Santiago de Compostela, Spain"},{"name":"Department of Surgery and Medical-Surgical Specialties, Faculty of Optics and Optometry, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"Instituto Galego de Oftalmolox\u00eda (INGO), Hospital Provincial de Conxo, 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogelio","family":"Leira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Cl\u00ednico Universitario, Universidad de Santiago de Compostela, 15705 Santiago de Compostela, 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