Korean J Pain 2021; 34(1): 47-57
Published online January 1, 2021 https://doi.org/10.3344/kjp.2021.34.1.47
Copyright © The Korean Pain Society.
1Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China
2Institute of Neuroscience and Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
3Department of Spine Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
4Department of Pathology, Vocational Technical School of Nanhai, Foshan, China
Correspondence to:Yi Zhong
Key Laboratory of Neuroscience, School of Basic Medical Science, Guangzhou Medical University, Xinzao, Pangyu District, Guangzhou 511436, China
*These authors contributed equally to this work.
Received: August 26, 2020; Revised: November 16, 2020; Accepted: November 19, 2020
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 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-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: Cytokines, Hyperalgesia, Intervertebral Disc, Microglia, Neuralgia, NF-kappa B, Nucleus Pulposus, Pain, Toll-Like Receptor 4.