The effects of pulsed radiofrequency stimulation on mitochondrial function in neurons: a mini review

Pulsed radiofrequency (PRF) stimulation is a widely used clinical intervention for neuropathic pain. Unlike continuous radiofrequency (CRF) ablation, PRF is non-destructive, yet its precise mechanism of action remains under debate. Emerging evidence suggests a fundamental role of mitochondrial modulation in driving both analgesia and nerve regeneration. To synthesize the literature investigating PRF effects on neuronal mitochondrial function, a scoping review was conducted across five databases (MEDLINE, Embase, CENTRAL, Web of Science, PubMed) from inception to February 2, 2026. From 141 initial records, 10 experimental studies met the inclusion criteria for narrative synthesis. Four studies comparing PRF with CRF confirmed that while CRF induces severe mitochondrial pathology (swelling, cristolysis, and necrosis), PRF preserves mitochondrial ultrastructure. The remaining six studies identified specific bioenergetic mechanisms. PRF was found to actively decrease mitochondrial membrane potential (ΔΨm) while increasing cytosolic ATP, effectively reversing the bioenergetic profile associated with central sensitization. Furthermore, PRF treatment was associated with mitochondrial hyperplasia; while hypothesized to represent compensatory biogenesis supporting structural repair, confirmation of these exact pathways is still needed. PRF stimulation appears to exert its effects, in part, through multiple mitochondrial mechanisms: an acute analgesic phase mediated by depolarizing the mitochondrial membrane and reducing excitotoxic calcium influx, and a sub-acute neuroregenerative phase bioenergetically supported by the neuro-glial metabolic unit. Ultimately, further exploration into the specific mechanisms by which neuromodulation impacts mitochondrial health and function in neuropathies is warranted.