Pulsed Radiofrequency Modulates Pain Regulatory Gene Expression Along the Nociceptive Pathway

Abstract

Background: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing electromagnetic energy aimed to relieve neuropathic pain. This is the first study examining the modulated expression of pain regulatory genes following the induction of the spared nerve injury (SNI) pain model and subsequently treated with PRF therapy. Objectives: The present study investigated the behavioral efficacy of PRF therapy in rats exhibiting sciatic nerve injury and examined gene expression changes in the sciatic nerve, ipsilateral L5 dorsal root 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 sham surgery was also performed as a control group. After 3 days development of the SNI model, an RF electrode was applied to the sciatic nerve proximal to the site of injury and stimulated for 3 minutes. 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 spinal cord) were assessed 24 hours post-PRF therapy. Results: It was observed that the mechanical allodynia, induced by SNI model, was reversed to control values within 24 hours post-PRF therapy. Additionally, modulated expression of pain regulatory genes was observed after induction of the SNI model. Following PRF therapy, expression of many of these genes returned to control values (sham) in each of the tissues tested. Increased proinflammatory gene expression, such as TNF-α and IL-6, observed in the sciatic nerve (site of injury) in the SNI group was returned to baseline values following PRF therapy. Up-regulation of GABAB-R1, Na/K ATPase, and 5-HT3r as well as down regulation of TNF-α and IL-6 were also observed in the DRG in the SNI-PRF group relative to the SNI group. Up-regulation of Na/K ATPase and 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 better determine the mechanism with no long-term data at this time. Protein expression was not assessed in addition to gene expression changes. Conclusion: These results indicate that the electromagnetic energy applied via PRF therapy influences the reversal of behavioral and molecular effects of hypersensitivity developed from a peripheral 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