Work

Chronic cervical instability in mice and rats: a reproducible model to simulate human intervertebral disc degeneration

Year: 2025

Type: article

Abstract: Background: Chronic low-back pain, a leading cause of global disability, is closely linked to intervertebral disc degeneration (IVDD). Traditional animal models have faced challenges in replicating the gradual, chronic nature of human IVDD. Objective: To address these limitations, we aimed to develop a novel mouse model of cervical spine instability that more accurately mimics the progressive degeneration observed in humans. Animals: This study used 48 male Sprague-Dawley rats (3 months old, weighing 230 ± 20 g) and 48 male C57BL/6 mice (12 weeks old, weighing 20 ± 2 g). Methods: magnetic resonance imaging (MRI), histological staining (H&E and Safranin O-fast green), immunofluorescence and western blot analyses at 4, 8, and 12 weeks post-operation. Results: MRI findings demonstrated progressive degeneration at the C4/5, C5/6, and C6/7 levels, with the most pronounced changes observed at 4 and 8 weeks post-surgery and partial recovery at 12 weeks. H&E and Safranin O staining confirmed significant cellular loss, structural disorganization, and proteoglycan depletion in the affected discs. Immunofluorescence staining revealed a progressive decrease in collagen type II and aggrecan expression over time. Conversely, collagen type I expression increased, indicating a shift toward fibrosis. Western blot analysis confirmed elevated levels of oxidative stress markers (albumin and AOPPs), matrix metalloproteinases (MMP3 and MMP13), senescence markers (p53, p21, p16), and inflammatory cytokines (IL-1β, TNF-α) at 4 and 8 weeks, with a partial decline by 12 weeks. Conclusions: This innovative cervical instability model not only minimizes the risk of nerve injury and reduces animal stress compared to previous models but also offers a reproducible and ethically sound platform for investigating IVDD pathogenesis and testing potential therapeutic interventions.

Source: PeerJ

DOI: 10.7717/peerj.20465