Pain Hypersensitivity in a Mouse Model of Marfan Syndrome
Kordikowski, Rebecca (Institut de Recerca Sant Pau)
Pereira Coutinho, Joana (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Martínez-Martel, Ignacio (Institut de Recerca Sant Pau)
Penas Pérez, Clara (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Martín-Mur, Beatriz (Universitat de Barcelona)
Pérez, Belén (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Jiménez Altayó, Francesc (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date:	2026
Description:	25 pàg.
Abstract:	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-β1 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 MF.
Grants:	Agencia Estatal de Investigación PID2020-113634RB-C22 Generalitat de Catalunya 2021/SGR-00969 Instituto de Salud Carlos III PI21/00592 Generalitat de Catalunya 2021/SGR-00548
Rights:	Aquesta url de drets no existeix a la base de dades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Pain ; Marfan syndrome ; Thoracic aorta aneurysm ; Neuroinflammation ; Oxidative stress ; Muscular deficits
Published in:	Antioxidants, Vol. 15, Num. 1 (January 2026) , art. 80, ISSN 2076-3921

DOI: 10.3390/antiox15010080

25 p, 2.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles