Objective:

To review RNA biomarker classes and propose a clinically deployable testing system for the diagnosis, stratification, and treatment monitoring of neuropathic pain, noting the absence of FDA-approved RNA-based biomarkers for pain.

Approach:

• RNA Biomarker Classes: The review focuses on mRNA, miRNA, lncRNA, RNA editing, and RNA modifications as potential biomarkers for neuropathic pain.
• Transcriptomic Evidence: Evidence from immune-cell transcriptomic meta-analysis and gene expression patterns in dorsal root ganglion and central nervous system is synthesized.
• Clinical and Translational Evidence: Clinical studies supporting miRNA biomarkers and lncRNA regulatory nodes are discussed.
• Epitranscriptomic Modifications: The role of m6A modifications in regulating pain-related mRNA is examined.
• Emerging RNA Workflow Technology: A new RNA workflow technology pathway leveraging rapid low-input RNA assays is explained.

Key Findings:

• RNA-based biomarkers may provide a biologically sound and objective approach to understanding and managing neuropathic pain, but current evidence is theoretical and lacks validation.
• Current pain assessment tools are subjective and contribute to variability in treatment response.
• No FDA-approved RNA-based biomarkers for pain exist, and current evidence remains at the theoretical model stage.

Interpretation:

Validation through clinical trials is necessary.

Limitations:

• Current evidence is theoretical and lacks validation through in vivo or clinical trials.
• Subjectivity in existing pain assessment tools complicates diagnosis and treatment efficacy evaluation.

Conclusion:

Further research is needed for clinical application of RNA biomarkers.