{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:09:47Z","timestamp":1768316987194,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia e Innovaci\u00f3n and Agencia Estatal de Investigaci\u00f3n of Spain","award":["PID2020-113634RB-C22\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2020-113634RB-C22\/AEI\/10.13039\/501100011033"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021 SGR 00969"],"award-info":[{"award-number":["2021 SGR 00969"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), Uni\u00f3n Europea","award":["PI21\/00592"],"award-info":[{"award-number":["PI21\/00592"]}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2021 SGR 00548"],"award-info":[{"award-number":["2021 SGR 00548"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Marfan syndrome (MFS) is a genetic disorder caused by mutations in the fibrillin-1 (Fbn1) gene, leading to structurally abnormal elastic fibers and diverse clinical manifestations. Aortic root dilation represents the most serious threat, often requiring prophylactic surgical repair. Emerging evidence suggests that MFS patients experience increased pain sensitivity, contributing to functional impairment and reduced quality of life. Here, we used C57BL\/6 wild-type and Fbn1C1041G\/+ (MFS) mice to examine brain transcriptomics, aortic histology, nociceptive behaviors, grip strength, and spinal cord gene expression in both sexes at 2, 4, 6, 8, and 16 months of age. Transcriptomic analysis revealed reduced activation of pain-related pathways in young males and aged females, with a reversal in aged males, suggesting age- and sex-dependent differences in pain modulation. Behavioral testing showed progressive mechanical and thermal hypersensitivity in MFS mice, with cold allodynia as the earliest manifestation with late-onset muscle weakness. In the spinal cord of 16-month-old MFS mice, increased expression of key excitatory and nociceptive markers was observed, consistent with the pain hypersensitivity phenotype. In addition, aged female MFS mice exhibited elevated spinal expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and Nox4, whereas males showed increased transforming growth factor-\u03b21 and Nox1, reflecting distinct inflammatory and oxidative stress profiles. These findings demonstrate that Fbn1C1041G\/+ mice reproduce pain hypersensitivity and muscle deficits observed in MFS patients, supporting their use as a preclinical model. Our results suggest that enhanced spinal excitatory\/nociceptive signaling, together with neuroinflammation and oxidative stress, contributes to sex- and age-specific pain mechanisms in MFS.<\/jats:p>","DOI":"10.3390\/antiox15010080","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:01:29Z","timestamp":1767862889000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pain Hypersensitivity in a Mouse Model of Marfan Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1085-9478","authenticated-orcid":false,"given":"Rebecca","family":"Kordikowski","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau (IR SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2097-7883","authenticated-orcid":false,"given":"Joana","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Pharmacology, Therapeutics, and Toxicology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3100-8293","authenticated-orcid":false,"given":"Ignacio","family":"Mart\u00ednez-Martel","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau (IR SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0554-3832","authenticated-orcid":false,"given":"Clara","family":"Penas","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola Del Vall\u00e8s, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas (RED-TERAV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6006-3295","authenticated-orcid":false,"given":"Beatriz","family":"Mart\u00edn-Mur","sequence":"additional","affiliation":[{"name":"Centro Nacional de An\u00e1lisis Gen\u00f3mico (CNAG), Universitat de Barcelona, 08028 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-1704","authenticated-orcid":false,"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Pharmacology, Therapeutics, and Toxicology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-2041","authenticated-orcid":false,"given":"Francesc","family":"Jim\u00e9nez-Altay\u00f3","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Department of Pharmacology, Therapeutics, and Toxicology, School of Medicine, Universitat Aut\u00f2noma de Barcelona, 08193 Cerdanyola del Vall\u00e8s, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-8457","authenticated-orcid":false,"given":"Olga","family":"Pol","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut de Recerca Sant Pau (IR SANT PAU), Sant Quint\u00ed 77-79, 08041 Barcelona, Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. 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