Dysregulation of the Inflammatory Mediators in the Multifidus Muscle After Spontaneous Intervertebral Disc Degeneration SPARC-null Mice is Ameliorated by Physical Activity

Study Design. A longitudinal case-control animal model. Objective. The aim of this study was to investigate the inflammatory pathways active in the multifidus muscle after spontaneous intervertebral disc degeneration (IDD), and whether these IDD-related muscle changes can be ameliorated by exercise. Summary of Background Data. A pro-inflammatory response is present in the multifidus muscle after an intervertebral disc lesion and has been proposed to drive the structural alterations present during low back pain. However, it is not known whether spontaneous IDD produces an inflammatory response. Furthermore, exercise/physical activity produces a strong anti-inflammatory response, but its effectiveness in ameliorating inflammation in the multifidus is unknown. We assessed the inflammatory profile of the multifidus and the effectiveness of physical activity as a treatment using an animal model of spontaneous model of IDD. Methods. Wild-type and SPARC null mice that were sedentary or housed with a running wheel were used in this study. Multifidus muscle segments were harvested from L2-L6 from the mice at 9 months of age after they had undergone a magnetic resonance imaging (MRI) scan to determine levels with IDD. The inflammatory profile of the multifidus was examined using quantitative polymerase chain reaction (PCR) assays. Results. Spontaneous IDD in the SPARC-null mice caused a dysregulation of interleukin (IL)-1β, IL6, transforming growth factor-beta (TGFβ1), and adiponectin expression. More specifically, the proximity and degree of IDD was related to levels of IL-1β expression. Physical activity reduced the pro-inflammatory response to IDD in the multifidus. IL-1β, tumor necrosis factor (TNF), IL-10, adiponectin, and leptin levels were lower in the physically active group. Conclusion. These results reveal that spontaneous IDD causes dysregulation of the inflammatory pathways active in the multifidus muscle. These alterations were related to the severity of IDD and were prevented by physical activity. Level of Evidence: N/A

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