Pulsed Radiofrequency and Epigenetic Modulation of Pain Pathways: A Systematic Review Based on Preclinical Evidence

Area of Science:

• Neurology
• Pain Management
• Molecular Biology

Background:

• Pulsed radiofrequency (PRF) is a non-invasive neuromodulation technique for refractory neuropathic pain.
• Its precise mechanisms, particularly epigenetic regulation, are not fully understood.
• The dorsal root ganglion (DRG) and peripheral nerves are key targets in pain signaling and neuro-immune interactions.

Purpose of the Study:

• To review preclinical research on epigenetic and molecular alterations following PRF application to the DRG or peripheral nerves.
• To synthesize evidence regarding PRF's impact on gene expression and epigenetic modifications in pain pathways.

Main Methods:

• A systematic literature search was conducted across PubMed, Embase, and Scopus databases.
• Studies investigating direct epigenetic modifications or gene/protein expression changes post-PRF were included.
• Risk of bias was assessed using the JBI checklist for animal studies.

Main Results:

• Seventeen rodent studies were analyzed, with one showing PRF reversed histone hypoacetylation at the Kcc2 locus.
• PRF application modulated neurotrophic factors, reduced pro-inflammatory cytokines, and normalized sensory neuron excitability.
• DRG PRF primarily attenuated spinal microglial/MAPK signaling, while sciatic nerve PRF focused on DRG channel and neuropeptide normalization.

Conclusions:

• Preclinical findings suggest PRF works by reducing neuro-immune signaling and restoring inhibitory tone.
• Direct epigenetic evidence is limited to a single study, and no human epigenetic biomarkers have been identified.
• Future research should standardize PRF parameters, conduct time-course and multi-omic studies, and include molecular endpoints in clinical trials.