Nuclear Factor Kappa B Increases CX3CR1 Expression in BV-2 Microglial Cells and Aggravates Neuropathic Pain

Abstract Background: Nuclear factor kappa B is well-known for its pro-neuroinflammation function. However, it remains unknown how it increases the expression of inflammatory factors, which in turn promotes neuropathic pain. Here we investigated its role in the development of neuropathic pain in rats using a sciatic chronic constriction injury model and examined its effect in up-regulating CX3CR1 expression in BV-2 microglial cells induced by tumor necrosis factor-alpha. Methods : The sciatic nerve chronic constriction injury (CCI) model was used to induce neuropathic pain in rats. Mechanical stimuli and radiant heat were used to evaluate mechanical allodynia and thermal hyperalgesia. The pain related behavioral effect of Nuclear factor kappa B was accessed after intrathecal administration of pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor. BV-2 microglia activation was induced by tumor necrosis factor-alpha incubation, and the levels of inflammatory factors and CX3CR1 were assessed. Results: Intrathecal infusion of pyrrolidine dithiocarbamate, a nuclear factor kappa B inhibitor, at 100 or 1000 pmol/d prevented the development of mechanical and thermal hyperalgesia and inhibited spinal microglial activation and tumor necrosis factor-alpha expression. In addition, phospho-p65 expression revealed that transient nuclear factor kappa B activation in BV-2 microglial cells was triggered by tumor necrosis factor-alpha.and increased CX3CR1 mRNA and protein expression. Pyrrolidine dithiocarbamate inhibited the tumor necrosis factor-alpha-inducedexpression of CX3CR1. Conclusion: These results suggested that the activation of nuclear factor kappa B pathway might enhance spinal microglial activation and tumor necrosis factor-alpha expression in neuropathic pain and the phosphorylation of p65 might be responsible for tumor necrosis factor-alpha-induced CX3CR1 expression in BV-2 microglial cells.