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

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.

Clear differences in cerebrospinal fluid proteome between women with chronic widespread pain and healthy women – a multivariate explorative cross-sectional study

“…This was found to be due to downregulation of IGF2 and the inhibition of ERK1/2 activity in microglial cells. 62 …”

The Levels of Insulin‐Like Growth Factor in Patients with Myofascial Pain Syndrome and in Healthy Controls

“…[14][15][16] Although the role of IGF-2 in neuropathic pain is largely unknown, there is some evidence for anti-allodynic effect because of downregulation of IGF-2. 17 However, to our knowledge no study has investigated the levels of IGF-1 and IGF-2 in MPS patients. Furthermore, studies have documented a higher prevalence of pain-related disorder in women than men, [18][19][20] suggesting that gender differences in the levels of biomarkers may be related to injury or repair mechanisms.…”

Pulsed radiofrequency attenuates diabetic neuropathic pain and suppresses formalin-evoked spinal glutamate release in rats

“…In a spinal nerve ligation model, PRF significantly diminished nerve ligation-induced mechanical allodynia and thermal by downregulating p38 and ERK activation 33 and TNF production. In a spared nerve injury model, PRF can decrease mechanical and cold pain behaviours for more than 28 d and suppress the activation of ERK in the spinal cord 34. All of these reports support that the analgesic mechanisms of PRF are closely associated with the suppression of MAPK activation.…”