Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

There are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. SM/J mice, a poor healer inbred strain, presented a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammation with altered extracellular matrix regulation in the dorsal root ganglia and spinal cord. There were increased T cells in the vertebral marrow, and cytometry by time-of-flight analysis showed increased splenic CD8+ T cells, nonspecific activation of CD8+ memory T cells, and enhanced interferon-γ production in the myeloid compartment. Single-cell RNA sequencing of peripheral blood mononuclear cells showed more B cells, with lower proportions of T cells, monocytes, and granulocytes. This study highlights the contribution of genetic background and aging to increased susceptibility of spontaneous intervertebral disc herniations in a clinically relevant murine model.

URI

http://hdl.handle.net/10400.14/54555

Citation

Novais, E. J., Ottone, O. K., Brown, E. V., & Madhu, V. et al. (2025). Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice. Science advances, 11(17), Article eado6847. https://doi.org/10.1126/sciadv.ado6847