Genetic background and aging-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. We demonstrate that SM/J mice show 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 ECM regulation in the DRG and spinal cord. There were increased T cells in the vertebral marrow, and CyTOF analysis showed increased splenic CD8+ T cells, nonspecific activation of CD8+ memory T cells, and enhanced IFN-γ production in the myeloid compartment. ScRNA-seq of PBMCs 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 disc herniations and clinically relevant pain phenotypes in SM/J mice. DRG and AF tissue were dissected from lumbar discs from BL6 and SM/J mice (n=4-6 per group). RNA extraction and hybridization on Affymetrix microarrays.