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  4. RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation

RNA-seq of spinal cord from nerve-injured rats after spinal cord stimulation

Molecular Pain, 2018 · DOI: 10.1177/1744806918817429 · Published: November 12, 2018

NeurologyPain ManagementGenetics

Simple Explanation

Spinal cord stimulation (SCS) is a treatment for neuropathic pain, but how it works on a molecular level isn't well understood. This study used RNA sequencing (RNA-seq) to examine gene expression changes in the spinal cord of nerve-injured rats after SCS treatment. The study found that SCS increased the expression of immune response genes and repressed the transcription of synaptic signaling genes. These transcriptional changes may explain the therapeutic effects of SCS and could help identify new targets for pain treatment. Specifically, SCS downregulated several genes encoding scaffold proteins located on the postsynaptic membrane in nerve-injured rats after SCS for the first time, which may impact neurotransmission and synaptic efficacy associated with central sensitization.

Study Duration
5 weeks
Participants
12 adult male and female Sprague-Dawley rats
Evidence Level
Not specified

Key Findings

  • 1
    Repetitive SCS further increases many existing upregulated immune responses in chronic constrictive injury rats, including transcription of cell surface receptors and activation of non-neuronal cells.
  • 2
    Repetitive SCS represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density.
  • 3
    SCS was associated with decreased expression of Slc6a11. Thus, a decrease of Slc6a11 expression by SCS may be a previously uncharacterized mechanism that promotes pain inhibition through increased availability of GABA within the synaptic cleft.

Research Summary

This study used RNA-seq to identify gene expression changes in the spinal cord of nerve-injured rats after repetitive conventional spinal cord stimulation (SCS) treatment. The RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive SCS, including transcription of cell surface receptors and activation of non-neuronal cells. The study also demonstrates that repetitive SCS represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density.

Practical Implications

Therapeutic Targets

The results may help identify new therapeutic targets for improving the efficacy of conventional SCS and other chronic pain treatments.

Mechanism Understanding

Transcriptional studies will help explain physiological changes that occur in the spinal cord following repeated SCS after nerve injury.

SCS Efficacy Improvement

Future attempts to increase the therapeutic effects of SCS may involve the combination of conventional SCS with other treatments aimed at specific transcriptional and epigenetic targets.

Study Limitations

  • 1
    Only a small number of genes were differentially expressed between sexes, and male and female rats showed similar GO biological processes associated with SCS.
  • 2
    The correlation coefficient measures only the degree of linear association between two variables and not causal relationships.
  • 3
    The mechanisms leading to changes in gene expression in distal spinal segments after SCS are unknown.

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