The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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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

  • Zhu, Lirong (Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University) ;
  • Huang, Yangliang (Department of Spine Surgery, First Affiliated Hospital of Sun Yat-Sen University) ;
  • Hu, Yuming (Department of Pathology, Vocational Technical School of Nanhai) ;
  • Tang, Qian (Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University) ;
  • Zhong, Yi (Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University)
  • Received : 2020.08.26
  • Accepted : 2020.11.19
  • Published : 2021.01.01
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Abstract

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-κB) 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 proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. Results: Spinal expression of TLR4 and p-NF-κB (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-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. Conclusions: The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

Keywords

Acknowledgement

This work was supported by grants from the Characteristic Innovation Project of Ordinary University of Guangdong Province (No. 2019KTSCX145), Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515010131), National Natural Science Foundation of China (No. 81600968).

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