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A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome

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Abstract

Inhibition of immune and inflammatory reaction induced by the expose of nucleus pulposus (NP) could effectively ameliorate neuropathic pain in the lumbar disc herniation. Maresin1 (MaR1), as a macrophage-derived mediator of inflammation resolution, displayed potent anti-inflammatory action. In the present study, we attempted to elucidate the impact of MaR1 on radicular pain and the interaction with NLRP3 inflammasome. We established a rat model of non-compressive lumbar disc herniation and different administration (MaR1 or Caspase-1 inhibitor) was given to them. The paw withdrawal latency (PWL) and paw withdrawal thresholds (PWTs) were observed to assess pain behaviors. The spinal cord horns were collected and the levels of IL-1β and IL-18 were measured by ELISA. The mRNA and protein expression levels of NLRP3 inflammasome components were tested by RT-PCR, western blot and immunohistochemistry. The endogenous MaR1 levels of the spinal cord were analyzed using LC–MS/MS. The application of NP in the models lead to mechanical and thermal hypersensitivity, increased IL-1β and IL-18 levels and expressions of NLRP3 inflammasome components, which were reversed markedly by administration of MaR1. Caspase-1 inhibition also improved mechanical hypersensitivity, decreased the expressions of inflammatory cytokines and restrained the activation of inflammasome. Meanwhile, Caspase-1 inhibitor promoted the endogenous MaR1 synthesis, which was hindered in the pain models. Altogether, our study indicated that the negative interaction between MaR1 and NLRP3 inflammasome mediated the inflammatory response in spinal dorsal horn, which involved in the pathogenesis of radicular pain.

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Data Availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgments

We thank Dr. Zhi-hua Liu and Dr. Lan-yu Zhang for the technical assistance.

Funding

This study was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81772443, 81972145).

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Author notes

  1. Yi-hao Wang and Yan Li have contributed equally to this work.

Authors and Affiliations

  1. Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, 324 Jingwu Road, Jinan, 250021, Shandong, China

    Yi-hao Wang, Jun-nan Wang, Qing-xiang Zhao, Shuang Wen, Si-cong Wang & Tao Sun

  2. Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, 266003, Shandong, China

    Yi-hao Wang

  3. Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China

    Yan Li

Authors
  1. Yi-hao Wang
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  4. Qing-xiang Zhao
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Contributions

YW and YL was responsible for carrying out the major part of the study, the statistical analyses and writing the manuscript. JW helped conducting the animal models and Western blot study. QZ helped carrying out the behavioral tests and Lipid mediator lipidomics assay. SW collected the tissues and carried out the ELISA study. SW carried out the real-time polymerase chain reaction. TS conceived and designed the study, and revised the manuscript.

Corresponding author

Correspondence to Tao Sun.

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The authors declare no conflicts of interest.

Ethical Approval

All the animal experiments of this study were approved by Shandong University Animal Care and Use Committee.

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Written informed consent for publication was obtained from all participants.

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Wang, Yh., Li, Y., Wang, Jn. et al. A Novel Mechanism of Specialized Proresolving Lipid Mediators Mitigating Radicular Pain: The Negative Interaction with NLRP3 Inflammasome. Neurochem Res 45, 1860–1869 (2020). https://doi.org/10.1007/s11064-020-03050-x

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  • DOI: https://doi.org/10.1007/s11064-020-03050-x

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