Pulsed Radiofrequency Modulates Pain Regulatory Gene Expression Along the Nociceptive Pathway

Background: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing electromagneticenergy aimed to relieve neuropathic pain. This is the first study examining the modulated expressionof pain regulatory genes following the induction of the spared nerve injury (SNI) pain model andsubsequently treated with PRF therapy.Objectives: The present study investigated the behavioral efficacy of PRF therapy in rats exhibitingsciatic nerve injury and examined gene expression changes in the sciatic nerve, ipsilateral L5 dorsalroot ganglia (DRG), and spinal cord.Study Design: A randomized, experimental trial.Setting: Department of Biological Sciences, Illinois State University and Department of Psychology,Illinois Wesleyan University.Methods: An SNI model was used in male Sprague-Dawley rats (weight 260-310 g). A shamsurgery was also performed as a control group. After 3 days development of the SNI model, anRF electrode was applied to the sciatic nerve proximal to the site of injury and stimulated for 3minutes. The response to mechanical stimuli was assessed throughout the duration of the study.Furthermore, changes in gene expression along the nociceptive tract (sciatic nerve, DRG, and spinalcord) were assessed 24 hours post-PRF therapy.Results: It was observed that the mechanical allodynia, induced by SNI model, was reversedto control values within 24 hours post-PRF therapy. Additionally, modulated expression of painregulatory genes was observed after induction of the SNI model. Following PRF therapy, expressionof many of these genes returned to control values (sham) in each of the tissues tested. Increasedproinflammatory gene expression, such as TNF-α and IL-6, observed in the sciatic nerve (site ofinjury) in the SNI group was returned to baseline values following PRF therapy. Up-regulation ofGABAB-R1, Na/K ATPase, and 5-HT3r as well as down regulation of TNF-α and IL-6 were alsoobserved in the DRG in the SNI-PRF group relative to the SNI group. Up-regulation of Na/K ATPaseand c-Fos was found in the spinal cord following PRF treatment relative to the SNI group.Limitations: Immediate changes in gene expression were observed at 24 hours to betterdetermine the mechanism with no long-term data at this time. Protein expression was not assessedin addition to gene expression changes.Conclusion: These results indicate that the electromagnetic energy applied via PRF therapyinfluences the reversal of behavioral and molecular effects of hypersensitivity developed from aperipheral nerve injury.Key words: Pulsed radiofrequency, PRF; spared nerve injury, SNI; electromagnetic stimulation;Sprague-Dawley, rat; withdrawal threshold; mechanical allodynia, Von Frey; gene expression;nociceptive pathway; electroneuromodulation; cytokines