Recent animal studies have discovered dysregulation of local inflammatory activity as a novel mechanism to explain fat and connective tissue accumulation in the multifidus muscle in association with intervertebral disc (IVD) degeneration/injury. This study aimed to test whether similar mechanisms are active in humans by investigation of whether expression of inflammatory genes in the multifidus muscle differed between individuals with low and high levels of intra-muscular fat in the muscle. The secondary aims were to compare inflammatory gene expression in the intra-muscular, subcutaneous and epidural fat between groups.
Muscle and fat were procured from 24 individuals undergoing spine surgery for IVD herniation. Gene expression was quantified using qPCR assays. Participants were allocated to high- and low-fat infiltration groups based on clinical assessment of multifidus fat using Kjaer grading of MRI.
TNF expression in the multifidus muscle was greater in participants with high rather than low levels of fat infiltration. This group also had greater expression of leptin, but lower arginase-1 (marker of anti-inflammatory M2 macrophages) in intra-muscular and subcutaneous adipose tissue, and greater expression of TNF, adiponectin and nitric oxide synthase 2 (marker of pro-inflammatory M1 macrophages) in epidural fat.
The results support the hypothesis that IVD degeneration is associated with dysregulation of the inflammatory state of the local multifidus muscle, which provides initial evidence for translation of some, but not all, observations from recent animal studies to humans. Discovery of inflammatory dysregulation in epidural adipose tissue has potential for broad impact on tissue health and LBP symptoms.
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PWH has a Senior Principal Research Fellowship from the National Health and Medical Research Council (NHMRC) of Australia (APP1102905). The study was partly funded by a NHMRC Program Grant (APP1091302). XC is supported by an Australian Government RTP award and by the ISSLS travelling Fellowship 2018. The funding source did not play any role in investigation.
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James, G., Chen, X., Diwan, A. et al. Fat infiltration in the multifidus muscle is related to inflammatory cytokine expression in the muscle and epidural adipose tissue in individuals undergoing surgery for intervertebral disc herniation. Eur Spine J (2020). https://doi.org/10.1007/s00586-020-06514-4
- Intervertebral disc herniation
- Multifidus muscle
- Fat infiltration
- Pro-inflammatory cytokine
- Tumour necrosis factor