IL-10 alleviates radicular pain by inhibiting TNF-α/p65 dependent Nav1.7 up-regulation in DRG neurons of rats

Abstract

BackgroundLumbar disc herniation (LDH) may induce radicular pain, the upregulation of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) contributes to radicular pain by generating ectopic discharge of neurons, but the mechanism is unclear. Previously, we reported pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) up-regulated VGSCs in diabetic neuropathy. In this study, we explored the effect of anti-inflammatory cytokine interleukin-10 (IL-10) on radicular pain and the possible mechanisms. MethodsRat model of LDH was induced by implanting autologous nucleus pulposus (NP). Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. IL-10 and TNF-α level in DRG and cerebrospinal fluid (CSF) were assessed by Enzyme-linked immunosorbent assay (ELISA). IL-10 was intrathecally delivered for 12 days. The expression of IL-10R1 and sodium channel Nav1.7 was displayed by immunofluorescence staining. The protein level of TNF-α and p-p65 was measured by western blotting. ResultsNP implantation increased Nav1.7 expression in DRG neurons, decreased IL-10 level and increased TNF-α level in DRG and CSF. IL-10 significantly alleviated pain behaviors of rats with NP. IL-10R1 was co-localized with neurons but not with satellite cells in DRG. IL-10 decreased Nav1.7 and TNF-α/p-p65 expression in DRG of rats with NP. Co-administration of TNF-α with IL-10 counteracted the effect of IL-10 on pain behaviors, Nav1.7 and TNF-α/p-p65 expression of rats with NP. ConclusionsThe study revealed that IL-10 alleviated radicular pain by inhibiting TNF-α/p-p65 dependent Nav1.7 up-regulation in DRG neurons.