Long-Term Anti-Allodynic Effect of Immediate Pulsed Radiofrequency Modulation through Down-Regulation of Insulin-Like Growth Factor 2 in a Neuropathic Pain Model.

Chun-Chang Yeh,Billy Huh,Chen-Hwan Cherng,Chi-Jung Huang,Chih-Shung Wong,Hsiao-Lun Sun,Chih-Cheng Chien,Jinn-Shyan Wang

doi:10.3390/ijms161126013

Abstract

Pulsed radiofrequency (PRF) is effective in the treatment of neuropathic pain in clinical practice. Its application to sites proximal to nerve injury can inhibit the activity of extra-cellular signal-regulated kinase (ERK) for up to 28 days. The spared nerve injury (SNI)+ immPRF group (immediate exposure to PRF for 6 min after SNI) exhibited a greater anti-allodynic effect compared with the control group (SNI alone) or the SNI + postPRF group (application of PRF for 6 min on the 14th day after SNI). Insulin-like growth factor 2 (IGF2) was selected using microarray assays and according to web-based gene ontology annotations in the SNI + immPRF group. An increase in IGF2 and activation of ERK1/2 were attenuated by the immPRF treatment compared with an SNI control group. Using immunofluorescent staining, we detected co-localized phosphorylated ERK1/2 and IGF2 in the dorsal horn regions of rats from the SNI group, where the IGF2 protein predominantly arose in CD11b- or NeuN-positive cells, whereas IGF2 immunoreactivity was not detected in the SNI + immPRF group. Taken together, these results suggest that PRF treatment immediately after nerve injury significantly inhibited the development of neuropathic pain with a lasting effect, most likely through IGF2 down-regulation and the inhibition of ERK1/2 activity primarily in microglial cells.

Highlights

Pulsed radiofrequency (PRF) is effective for some types of chronic intractable pain [1,2,3,4,5,6,7,8,9]
In the spared nerve injury (SNI) group, we found that phosphorylated ERK1/2 co-localized with Insulin-like growth factor 2 (IGF2) (Figure 4A), where IGF2 immunoreactivity was mainly found in spinal microglial and neuronal cells (Figure 5A,B)
Results from our study indicated that immPRF treatment after nerve injury mediated inhibition of SNI-induced IGF2, and ERK1/2 activation via spinal microglia may be a possible mechanism underlying its inhibitory action on SNI-induced neuropathic pain

Summary

Introduction

Pulsed radiofrequency (PRF) is effective for some types of chronic intractable pain [1,2,3,4,5,6,7,8,9]. Unlike conventional high-temperature radiofrequency, PRF can deliver a brief high-frequency electrical stimulation near a dorsal root ganglion (DRG) or a sensory nerve without significant nerve damage [10]. PRF application adjacent to a DRG or sensory nerve might change biological activity of synaptic transmission, cell morphology, or c-Fos expression in the superficial dorsal horn of the spinal cord, with a trivial effect on nerve tissue [11,12,13]. Low-voltage PRF may attenuate mechanical allodynia and thermal hyperalgesia in a rat model of neuropathic pain produced by spinal nerve ligation (SNL) by affecting the phosphorylation of ERK [17]. Immediate PRF application to sites proximal to nerve injury significantly inhibited the development of neuropathic pain, accompanied by inhibited ERK activation in rats after spared nerve injury (SNI) [18]. The inhibition of ERK activation might be a novel target for the treatment of neuropathic pain [19,20,21]

Methods

Results

Conclusion