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Long Noncoding RNA SNHG5 Knockdown Alleviates Neuropathic Pain by Targeting the miR-154-5p/CXCL13 Axis

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Abstract

Neuropathic pain is an unneglectable pain condition with limited treatment options owing to its enigmatic underlying mechanisms. Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is involved in the progression of a spectrum of human cancers. However, its role in neuropathic pain remains undiscovered. In the present study, we established a mouse spinal nerve ligation (SNL) model, and a significant upregulation of SNHG5 was observed. Then we knocked down SNHG5 level in mouse L5 dorsal root ganglion (DRG) by delivering specific short hairpin RNA against SNHG5 with adenovirus vehicle. Mouse paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in response to mechanical stimuli was increased after SNHG5 knockdown, accompanied with decreased protein levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (IBA-1). Besides, SNHG5 directly modulated the expression of miR-154-5p, which was downregulated in SNL mice. MiR-154-5p inhibition abolished the effect of SNHG5 knockdown on mouse behavioral tests and GFAP and IBA-1 levels. In addition, we validated that C-X-C motif chemokine 13 (CXCL13) was a novel downstream target of miR-154-5p, and CXCL13 level was positively related to that of SNHG5 in SNL mice. In conclusion, our study demonstrated that SNHG5 knockdown alleviated neuropathic pain and inhibited the activation of astrocytes and microglia by targeting the miR-154-5p/CXCL13 axis, which might be a novel therapeutic target for neuropathic treatment clinically.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the Innovation and Entrepreneurship Training Program for College Students in Guizhou Province (Grant No. 20195200924).

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Author notes

  1. Mi Chen and Yang Yang contributed equally to the work.

Authors and Affiliations

  1. Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guizhou Province, No. 28 Guiyi Street, Guiyang, 550004, China

    Mi Chen, Yang Yang, Wenqi Zhang, Jinli Wu, Xiaohua Zou & Xianggang Zeng

  2. College of Anesthesia, Guizhou Medical University, Guizhou Province, Guiyang, 550004, China

    Xinning Li

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  1. Mi Chen
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  2. Yang Yang
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  3. Wenqi Zhang
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  7. Xianggang Zeng
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Contributions

XHZ and XGZ conceived and designed the experiments, MC and YY analyzed and interpreted the results of the experiments, WQZ, XNL and JLW performed the experiments.

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Correspondence to Xiaohua Zou or Xianggang Zeng.

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Chen, M., Yang, Y., Zhang, W. et al. Long Noncoding RNA SNHG5 Knockdown Alleviates Neuropathic Pain by Targeting the miR-154-5p/CXCL13 Axis. Neurochem Res 45, 1566–1575 (2020). https://doi.org/10.1007/s11064-020-03021-2

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