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

Background: Lumbar 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.

Methods: Rat 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.

Results: NP 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.

Conclusions: The study revealed that IL-10 alleviated radicular pain by inhibiting TNF-α/p-p65 dependent Nav1.7 up-regulation in DRG neurons.