Toll-Like Receptor 4/Nuclear Factor-Kappa B Pathway Is Involved In Radicular Pain By Encouraging Spinal Microglia Activation And Inflammatory Response In A Rat Model Of Lumbar Disc Herniation

Background: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-kappa B) in radicular pain and its possible mechanisms.Methods: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of pro and anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay.Results: Spinal expression of TLR4 and p-NF-kappa B (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-kappa B inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)1 beta, IL-6, tumor necrosis factor-alpha expression and increasing IL-10 expression in the spinal dorsal horn.Conclusions: The study revealed that TLR4/NF-kappa B pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.