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

Area of Science:

• Biomedical research
• Molecular biology
• Pain research

Background:

• Back pain following intervertebral disc (IVD) injury is a prevalent clinical issue.
• Prior investigations into early molecular changes post-IVD injury primarily employed a candidate marker strategy.

Purpose of the Study:

• To comprehensively analyze early molecular changes in injured intervertebral discs (IVDs) using a nonbiased approach.
• To correlate gene expression profiles with subsequent pain behavior following IVD injury.

Main Methods:

• Induced mouse tail IVD injury via needle puncture.
• Performed whole transcriptome analysis using RNASeq on injured and intact murine IVDs.
• Utilized bioinformatic methods for transcriptome comparison and assessed mechanical allodynia with the Von Frey method.

Main Results:

• Out of 17,722 genes, 7242 were differentially expressed (P.adj < 0.01) post-injury.
• Upregulated genes were enriched in leukocyte migration; TNF-alpha showed the most protein-protein interactions.
• Downregulated pathways were associated with pattern specification; mechanical allodynia persisted for 4 weeks.

Conclusions:

• RNASeq identified numerous early genes involved in inflammation and repair post-IVD injury.
• Observed mechanical allodynia was temporally linked to these gene expression changes.