Pulsed radiofrequency inhibits expression of P2X3 receptors and alleviates neuropathic pain induced by chronic constriction injury in rats

Abstract

Background:Pulsed radiofrequency (PRF) is a minimally invasive interventional technique that provides a novel and effective treatment strategy for neuropathic pain (NP). PRF is advantageous because it does not damage nerves and avoids sensory loss after treatment. At present, animal studies have demonstrated that PRF is safe and effective for relieving the NP associated with sciatic nerve damage in rats with chronic constriction injury (CCI). However, the mechanism through which this effect occurs is unknown. An increasing body of evidence shows that the expression of the P2X ligand-gated ion channel 3 (P2X3) receptor is closely related to NP; this study was to investigate whether the expression of this receptor is involved in NP relief due to PRF.Methods:A total of 36 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups: Sham group, CCI group, and PRF group. The right sciatic nerve was ligated in CCI group and PRF group to establish a CCI model; the right sciatic nerve was separated but not ligated in Sham group. On day 14 after the operation, PRF was administered to the ligated sciatic nerve in PRF group (42°C, 45 V, 2 min). A non-live electrode was placed at the exposed sciatic nerve for the rats in Sham and CCI groups. The hindpaw withdrawal threshold (HWT) and thermal withdrawal latency (TWL) were measured at the right hindpaw at different time points before and after PRF or sham therapy. On day 28 after treatment, the dorsal root ganglion (DRG) and spinal dorsal horn of the right L4–6 were harvested from each group to determine the mRNA and protein levels of the P2X3 receptor.Results:On day 28 after PRF treatment, the HWT (8.33 ± 0.67 g vs. 3.62 ± 0.48 g) and TWL (25.42 ± 1.90 s vs. 15.10 ± 1.71 s) were significantly higher in PRF group as compared to CCI group (P < 0.05). The mRNA expression of the P2X3 receptor in the DRG in PRF group was 23.7% lower than that in CCI group (P < 0.05), in the spinal dorsal horns in PRF group was 22.7% lower than that in CCI group (P < 0.05). The protein expression of the P2X3 receptor in the DRG in PRF group was 27.8% lower than that in CCI group (P < 0.05), in the spinal dorsal horns in PRF group was 35.6% lower than that in CCI group (P < 0.05).Conclusion:PRF possibly reduces NP in CCI rats by inhibiting the expression of the P2X3 receptor in the L4–6 DRG and spinal dorsal horns.

Efficacy of Pulsed Radiofrequency to Cervical Nerve Root for Postherpetic Neuralgia in Upper Extremity

“…Recent studies have found that PRF can produce neuromodulation and relieve trigeminal PHN (Ding et al, 2019). It has been found that PRF can inhibit the nociceptive-induced release of excitatory neurotransmitters (Huang et al, 2016), reduce the expression of calcitonin gene-related peptide (CGRP) in DRG (Ren et al, 2018), inhibit the expression of P2 × 3 receptor in DRG and spinal dorsal horn (Fu et al, 2019), and reduce the expression of peripheral of pro-inflammatory cytokines (TNF-α and IL-6) and β-Catenin in spinal cord (Vallejo et al, 2013;Jiang et al, 2019); At the same time, PRF can up-regulate GDNF transcription and translation (Jia et al, 2016;Hailong et al, 2018), up-regulate GABAB-R1, Na/K ATPase and 5-HT3r gene expression (Vallejo et al, 2013), increase histone acetylation and KCC2 expression by modifying KCC2 and partially restored GABA synaptic function (Liu et al, 2017). The effect of neuromodulation is slow, so cervical nerve root PRF combined with nerve block was used.…”

Efficacy of Pulsed Radiofrequency or Short-Term Spinal Cord Stimulation for Acute/Subacute Zoster-Related Pain: A Randomized, Double- Blinded, Controlled Trial

“…PRF is usually believed to modulate the pain pathology with non-or minimal neural damage (9,10). Many animal studies have demonstrated that PRF is safe and effective treatment to reduce the NP (11,12). In clinical studies, PRF has also been widely proved to be effective for refractory NP, such as PHN, cervical or lumbar radicular pain, failed back surgery syndrome, and various peripheral neuralgia conditions (13)(14)(15).…”

CT-Guided Pulsed Radiofrequency at Different Voltages in the Treatment of Postherpetic Neuralgia

“…Compared to pre-surgery SF-36 scores, *P < 0.05; group B compared to group A, P < 0.05; group C compared to group A, ∂P < 0.05; group C compared to group B, #P < 0.05. Data expressed as the mean (median ± quartile range); group B compared to group A, P < 0.05; group C compared to group A, ∂P < 0.05; group C compared to group B, #P < 0.05. ion channels of the peripheral nerve cells such as the P2X ligandgated ion channel 3 and inhibits the peripheral sensitization of PHN (Cho et al, 2013;Liu et al, 2015;Fu et al, 2019). Research on central sensitization has found that PRF increases the expression of activating transcription factor 3 in pain conduction C and Aδ fibers, which activates the descending pain inhibitory system in the brainstem to achieve analgesic effects (Huang et al, 2017).…”