141: Peripheral Nerve Pulsed Radiofrequency Modulates Neuroimmune Mechanisms in Knee Osteoarthritis

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic secondary musculoskeletal pain, , , , , , , , , , Neuroimmunology

Background and Aims: Knee osteoarthritis (OA) pain comprises not only nociceptive pain caused by structural degeneration or synovitis, but also central sensitization leading to chronic pain [1]. Pulsed radiofrequency (PRF) is a neuromodulatory technique that delivers intermittent high-frequency electrical currents to peripheral nerves while maintaining tissue temperatures below 42 °C [2]. Although PRF has shown safety and analgesic efficacy in knee OA [3], its mechanisms remain unclear. Our previous studies demonstrated that sciatic nerve PRF suppresses MIA-induced arthritis and modulates axonal transport in C-fibers. This study aimed to elucidate the central neuroimmune mechanisms underlying PRF-induced analgesia in a mouse OA model.

Methods: Eight-week-old ddy mice were used. Knee OA was induced by intra-articular injection of monoiodoacetic acid (MIA; 0.75 mg in 10 μL saline) into the right knee under 2% isoflurane anesthesia (MIA group, n=12); sham-treated mice received saline alone (sham group, n=6). One week later, MIA-treated mice were randomly assigned to either pulsed radiofrequency treatment (MIA+PRF group, n=6) or electrode contact alone (MIA–PRF group, n=6) applied to the right sciatic nerve. PRF was delivered for 8 min at 2 Hz, 45 V, and a pulse width of 20 ms. Data were analyzed using one-way ANOVA with Tukey’s post hoc test.

Results: Mechanical withdrawal thresholds of the ipsilateral hind paw were significantly reduced after MIA injection but were restored following PRF treatment. In the ipsilateral L4 dorsal root ganglion (DRG), MIA-induced arthritis increased the number of CCL2-positive cells and the accumulation of F4/80-positive macrophages, both of which were attenuated by PRF. CGRP-positive area in the L4 DRG was also increased by MIA and reduced by PRF. In the ipsilateral L4 spinal dorsal horn, MIA elicited microglial activation, as indicated by increased Iba-1–positive area and morphology, as well as neuronal activation, evidenced by c-Fos–positive neurons. These changes were suppressed by PRF.

Conclusions: Our findings suggest that sciatic nerve PRF alleviates knee osteoarthritis pain by inhibiting axonal transport–dependent neuroinflammatory signaling along the peripheral–central pain pathway. PRF may disrupt axonal transport in C-fibers linking peripheral tissues and small DRG neurons, thereby reducing primary afferent input [4]. This reduction likely suppresses the production of inflammatory chemokines and neuropeptides such as CGRP in the DRG and limits macrophage infiltration. Consequently, diminished afferent signaling may attenuate microglial and neuronal activation in the spinal dorsal horn, thereby reducing central sensitization.

References: [1]Arendt-Nielsen L, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–581.
[2]Byrd D, et al. Pulsed radiofrequency for chronic pain: non-thermal neuromodulation via rapidly changing electrical fields. Curr Pain Headache Rep. 2008;12(1):37–41.
[3]Uematsu H, et al. Ultrasound-guided pulsed radiofrequency treatment of the saphenous nerve for refractory osteoarthritis-associated knee pain: a double-blind, placebo-controlled, randomized trial. Pain Physician. 2021;24:761–769.
[4]Erdine S, et al. Pulsed radiofrequency application in the treatment of chronic pain. Pain Pract. 2005;5(4):315–321.

Presenting Author: Momoyu Yamanaka
Submitting Author: Momoyu Yamanaka

Senior Author: Takeshi Yoshida

IASP 2026 Global Year theme of Neuropathic Pain: No

• Yoshihisa Koyama: PhD - Department of Neuroscience and Cell Biology, Graduate School of Medicine, The University of Osaka; Addiction Research Unit, Osaka Psychiatric Research Center
• Hiroshi Horiike: MD - Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, The University of Osaka; Center for Pain Management, The University of Osaka Hospital
• Ayako Takahashi: MD, PhD - Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, The University of Osaka; Center for Pain Management, The University of Osaka Hospital
• Yoichi Matsuda: MD, PhD - Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, The University of Osaka; Center for Pain Management, The University of Osaka Hospital
• Shoichi Shimada: MD, PhD - Department of Neuroscience and Cell Biology, Graduate School of Medicine, The University of Osaka; Addiction Research Unit, Osaka Psychiatric Research Center
• Takeshi Yoshida: MD, PhD - Department of Anesthesiology and Intensive Care Medicine, Graduate School of Medicine, The University of Osaka