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MicroRNA-204 silencing relieves pain of cervical spondylotic radiculopathy by targeting GDNF

Gene Therapy volume 27, pages 254–265 (2020)Cite this article

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Abstract

Cervical spondylosis may cause chronic neck pain, radiculopathy and/or myelopathy, and consequently results in severe brain damage. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for motoneurons. Accumulating microRNAs (miRNAs) have highlighted as critical regulators of GDNF signaling in the mediation of neuroinflammation and neuropathic pain. Hence, we performed this study to investigate the potential role of miR-204 in the neuropathic pain of cervical spondylotic radiculopathy (CSR) by targeting GDNF. A rat model of spinal cord compression (SCC) was established to stimulate a pathologic lesion. RT-qPCR and western blot assays characterized the downregulation of GDNF and the upregulation of miR-204 in spinal cord tissues of rats under the conditions of SCC. Moreover, miR-204 could directly target GDNF, as evidenced by dual-luciferase reporter gene assay. In order to elucidate the roles of miR-204 and GDNF in SCC-induced neuropathic pain, miR-204 sponge, GDNF, or shRNA against GDNF was introduced to the rats, followed by measurements for SCC-induced neuroinflammation and neuropathic pain. GDNF upregulation or miR-204 silencing was identified to reduce the spontaneous pain score, gait scores and cell apoptosis. Furthermore, GDNF upregulation or miR-204 silencing resulted in elevated amplitude of sensory-evoked potentials (SEPs), number of motoneurons, release of pro-inflammatory factors, TNF-α, and IL-1β in addition to an increase in the anti-inflammatory factor BDNF. Taken together, upregulation of GDNF induced by miR-204 silencing confers protection against SCC-induced pain in rat models, suggesting a potential therapeutic target for CSR treatment.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Authors and Affiliations

  1. Department of Anesthesiology, Shaoxing Paojiang Hospital, Shaoxing, 312000, PR China

    Wen-Sheng Shen

  2. Department of Anesthesiology, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, PR China

    Cun-Feng Li, Zhi-Shui Zhou, Nan-Nan Zhai & Lu-Ping Pan

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  1. Wen-Sheng Shen
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Shen, WS., Li, CF., Zhou, ZS. et al. MicroRNA-204 silencing relieves pain of cervical spondylotic radiculopathy by targeting GDNF. Gene Ther 27, 254–265 (2020). https://doi.org/10.1038/s41434-019-0114-3

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