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Bone mesenchymal stem cells attenuate radicular pain by inhibiting microglial activation in a rat noncompressive disk herniation model

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Abstract

Spinal disk herniation can induce radicular pain through chemical irritation caused by proinflammatory and immune responses. Bone marrow mesenchymal stem cells (BMSCs) are a unique type of adult stem cell with the functions of suppressing inflammation and modulating immune responses. This study was undertaken to observe the effect of intrathecal BMSCs on the treatment of mechanical allodynia and the suppression of microglial activation in a rat noncompressive disk herniation model. The model was induced by the application of nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). The study found that the use of NP in the DRG can induce abnormal mechanical pain, increase the contents of the proinflammatory factors TNF-α and IL-1β, decrease the content of the anti-inflammatory cytokine TGF-β1 and activate microglia in the spinal dorsal horns (L5) (P < 0.05). BMSC administration could increase the mechanical withdrawal thresholds dramatically, decrease the contents of IL-1β and TNF-α, increase the content of TGF-β1 significantly (P < 0.05) and inhibit microglial activation in the bilateral spinal dorsal horn. Our results indicate that BMSC administration can reduce mechanical allodynia and downregulate the expression of proinflammatory cytokines by inhibiting microglial activation in the spinal dorsal horn in a rat noncompressive disk herniation model.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant no. 81472071 and Grant no. 81301537) and the National High Technology Research and Development Program (“863” Program) of China (Grant no. 2013AA032203).

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  1. Xiaodong Huang, Weiheng Wang and Xilin Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China

    Xiaodong Huang, Weiheng Wang, Yanhai Xi, Jiangming Yu & Xiaojian Ye

  2. Department of Orthopaedics, Chengdu General Hospital of Chengdu Military Command Region, Chengdu, 610083, China

    Xilin Liu

  3. Department of Anatomy, Institute of Biomedical Engineering, Second Military Medical University, Shanghai, 200433, China

    Xiangqun Yang

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  1. Xiaodong Huang
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Contributions

Xiaodong Huang and Weiheng Wang carried out the major part of this study and wrote the manuscript. Xilin Liu helped with the animal model and behavioral testing. Yanhai Xi conducted a partial ELISA study. Jiangming Yu conducted a partial PCR study. Xiangqun Yang performed the statistical analyses and revised the manuscript. Xiaojian Ye conceived and designed the study. All authors read and approved the final manuscript.

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Correspondence to Xiangqun Yang or Xiaojian Ye.

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Dr. Xiaojian Ye is the main corresponding author of this paper.

Xiaojian Ye and Xiangqun Yang supported this project equally.

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Huang, X., Wang, W., Liu, X. et al. Bone mesenchymal stem cells attenuate radicular pain by inhibiting microglial activation in a rat noncompressive disk herniation model. Cell Tissue Res 374, 99–110 (2018). https://doi.org/10.1007/s00441-018-2855-5

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