Pulsed Radiofrequency 2 Hz Preserves the Dorsal Root Ganglion Neuron Physiological Ca(2+) Influx, Cytosolic ATP Level, Δψm, and pERK Compared to 4 Hz: An Insight on the Safety of Pulsed Radiofrequency in Pain Management

BACKGROUND: Pulsed radiofrequency (PRF) is beneficial for radicular pain and is commonly administered at pulse frequencies of 2 or 4 Hz. However, its effects on healthy neurons have not yet been widely studied. This study aims to determine the effect of PRF at 2 Hz and 4 Hz on the physiology of healthy dorsal root ganglion (DRG) neurons. METHODS: An in vitro experimental study was conducted using DRG neuron cultures divided into three groups. Control cells received no treatment, one cell group received 20 ms 2 Hz PRF for 360 s, and one cell group received a 4 Hz PRF 10 ms pulse for 360 s with similar energy. Ca(2+) influx, mitochondrial membrane potential (Δψm), cytosolic Adenosine triphosphate (ATP), and phosphorylated extracellular signal-regulated kinase (pERK) levels were measured. The data were analyzed using the One-Way ANOVA variance with α=5%. RESULTS: DRG neurons exposed to PRF 2 Hz did not experience a significant change in Ca(2+) influx, whereas PRF 4 Hz caused a significant decrease in Ca(2+) influx compared to the basal level. PRF at 2 Hz did not cause a change in Δψm, whereas PRF at 4 Hz caused a significant decrease in Δψm (p<0.05). Both 2 and 4 Hz PRF resulted in a significant elevation in cytosolic ATP concentration, but the 2 Hz PRF had a higher cytosolic ATP than the 4 Hz group (p<0.05). Both 2 and 4 Hz did not show a significant difference in pERK intensity with respect to the control (p>0.05), indicating that there was no significant neuron activation. CONCLUSION: Both frequencies did not significantly activate DRG neurons, but with similar energy delivery, PRF 2 Hz preserved the physiological properties of healthy neurons better than PRF 4 Hz did. A 2 Hz PRF is the preferred frequency in clinical applications for neuron-targeted therapy.