Transcriptomic analysis of differentially alternative splicing patterns in mice with inﬂammatory and neuropathic pain

Molecular Pain, 2024 · DOI: 10.1177/17448069241249455 · Published: April 1, 2024

Simple Explanation

Chronic pain is a widespread issue affecting a significant portion of the global population, with inflammatory and neuropathic pain being major types. Current treatments face challenges due to the complexity of the underlying factors. The study focuses on alternative splicing (AS), a process that increases protein diversity from a single gene. The study aims to analyze AS patterns in different tissues (brain, DRG, spinal cord) under inflammatory and neuropathic pain conditions. By identifying differentially alternatively spliced (DAS) genes, the researchers hope to provide new insights into the mechanisms of chronic pain and potentially guide the development of new diagnostic and therapeutic strategies.

Study Duration

Not specified

Participants

Nine 18-week-old BALB/c female mice

Evidence Level

Not specified

Key Findings

1
The study identified 6495 differentially alternatively spliced (DAS) genes in the mouse brain, dorsal root ganglion, and spinal cord tissue under inﬂammatory and neuropathic pain.
2
Shared DAS genes between inflammatory and neuropathic pain models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease.
3
A small proportion of differentially expressed genes (DEGs) also showed differential alternative splicing (DAS), supporting the idea that AS has a distinct regulatory pattern from transcriptional regulation.

Research Summary

The study analyzed alternative splicing (AS) patterns in mouse brain, dorsal root ganglion (DRG), and spinal cord tissues under inﬂammatory and neuropathic pain conditions to understand the molecular mechanisms of chronic pain. Researchers identified 6495 differentially alternatively spliced (DAS) genes and found that shared DAS genes between inflammatory and neuropathic pain models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. The study concludes that AS plays a crucial role in chronic pain and that identified DAS genes could potentially serve as candidates for classifying chronic pain or as targets for analgesia research.

Practical Implications

Drug Target Identification

The DAS DEGs identified in this study can serve as potential targets for developing new analgesic drugs.

Diagnostic Tool Development

These DAS DEGs could be used as biomarkers to classify different types of chronic pain at the gene level, improving diagnostic accuracy.

Personalized Medicine Approaches

Understanding the specific AS patterns in individual patients could lead to more personalized and effective pain management strategies.

Study Limitations

1
The study was conducted on mice, and further research is needed to validate these findings in humans.
2
The potential function and underlying regulatory mechanisms of many identified DAS DEGs are not yet fully understood.
3
Further investigation is required to understand the dynamic AS alteration in transcriptome associated with the development of chronic pain in SNI and CFA pain models.

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