Yuba T, Koyama Y et al. — Elucidation of the Treatment Mechanism of Pulsed Radiofrequency Based on its Antiinflammatory Effects
Scientific Reports (Nature Portfolio), September 2025
This Osaka University mouse study used a monoiodoacetic acid (MIA)-induced knee pain model to trace the precise mechanism behind PRF's anti-inflammatory effects. PRF was applied to the sciatic nerve — distant from the joint — and outcomes were assessed behaviorally, histologically, and biochemically.
Key findings:
- PRF improved weight-bearing and gait from day 10; the untreated group remained symptomatic through day 14
- PRF reduced synovial macrophage infiltration and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) without affecting cartilage loss — confirming an anti-inflammatory rather than chondroprotective effect
- PRF had no effect on healthy neurons, demonstrating selectivity for pathological tissue
- Retrograde tracer analysis showed PRF selectively impairs axonal transport in small C-fiber DRG neurons, reducing peripheral release of CGRP and substance P into the joint
- Administering both neuropeptide agonists together fully reversed PRF's effects — neither alone was sufficient, confirming their synergistic role
Significance: The most mechanistically precise PRF study to date, published in a high-impact Nature journal. It establishes a clear peripheral pathway — C-fiber axonal transport → CGRP/SP suppression → reduced neurogenic inflammation — complementing the central mechanisms described elsewhere in the literature.