Gene Expression Changes Precede Elevated Mechanical Sensitivity in the Mouse Intervertebral Disc Injury Model

Abstract

Background

Back pain after intervertebral disc (IVD) injury is a common clinical problem. Previous work examining early molecular changes post injury mainly used a candidate marker approach.

Methods

In this study, gene expression in the injured and intact mouse tail IVDs was determined with a nonbiased whole transcriptome approach and related to subsequent pain behavior. Mouse tail IVD injury was induced by a needle puncture. Whole murine transcriptome was determined by RNASeq. Transcriptomes of injured IVDs were compared with those of intact controls by bioinformatic methods. Mechanical allodynia was assessed by the Von Frey method.

Results

Among the 17,722 murine genes with meaningful expressions, 7242 genes were differentially expressed (P.adj ⟨ 0.01). Ontology study of upregulated genes revealed that leukocyte migration was the most enriched biological process, and network analysis showed that Tnfa had the most protein–protein interactions. The most enriched downregulated pathways were related to the pattern specification process. Mechanical allodynia persisted at the 4-week end point.

Conclusion

The RNASeq data revealed numerous early genes that participate in inflammation and repair processes post IVD injury. Mechanical allodynia followed these gene expression changes.