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Inhibition of MicroRNA-221 Alleviates Neuropathic Pain Through Targeting Suppressor of Cytokine Signaling 1

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Abstract

Neuropathic pain results in considerable trouble to people’s physical and mental health. The pathophysiological mechanisms underlying its occurrence and development remain unclear. A large number of experiments show that microRNAs (miRNAs) play a major role in the pathogenesis of neuropathic pain and neuroinflammation resulting from nerve injury. Among various miRNAs, microRNA-221 (miR-221) overexpression has been reported in a chronic constrictive injury (CCI)-induced rat model of neuropathic pain. However, the role of miR-221 in the regulation of neuropathic pain is unknown. In this study, we investigated the potential role and underlying mechanism of miR-221 in regulating neuropathic pain. Our findings show that miR-221 is overexpressed in the spinal cord and the isolated microglia of CCI rats. Intrathecal injection of a miR-221 inhibitor attenuated CCI-induced mechanical allodynia and thermal hyperalgesia, and reduced proinflammatory cytokine expression, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in CCI rats. Using a dual-luciferase reporter assay, we show that suppressor of cytokine signaling 1 (SOCS1), an important regulator of inflammation, is a direct target of miR-221. Treatment with the miR-221 inhibitor significantly inhibited the expression of SOCS1. Furthermore, the miR-221 inhibitor markedly suppressed the activation of nuclear factor-kappa B (NF-κB) and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Knockdown of SOCS1 in CCI rats abrogated the inhibitory effect of the miR-221 inhibitor on CCI-induced neuropathic pain and the NF-κB and p38 MAPK signaling pathways. Together, these results suggest that inhibition of miR-221 alleviates neuropathic pain and neuroinflammation through increasing SOCS1 and by inhibiting the NF-κB and p38 MAPK signaling pathways, indicating that miR-221 may be a promising molecular target for the treatment of neuropathic pain.

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Abbreviations

miR-221:

MicroRNA-221

SOCS1:

Suppressor of cytokine signaling 1

CCI:

Chronic constrictive injury

UTR:

Untranslated region

NF-κB:

Nuclear factor-kappa B

p38 MAPK:

p38 mitogen-activated protein kinase

TWL:

Thermal withdrawal latency

MWT:

Mechanical withdrawal threshold

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Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Jinshui District, Zhengzhou, 450014, People’s Republic of China

    Li Xia & Tieli Dong

  2. Department of Anesthesiology, Maternal and Child Health Hospital of Zhengzhou, Zhengzhou, 450000, China

    Yunlong Zhang

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  1. Li Xia
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  2. Yunlong Zhang
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  3. Tieli Dong
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Correspondence to Tieli Dong.

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All animal experimental procedures were approved by The Second Affiliated Hospital of Zhengzhou University Institutional Animal Care and Use Committee.

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The authors declare that they have no conflict of interest.

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Xia, L., Zhang, Y. & Dong, T. Inhibition of MicroRNA-221 Alleviates Neuropathic Pain Through Targeting Suppressor of Cytokine Signaling 1. J Mol Neurosci 59, 411–420 (2016). https://doi.org/10.1007/s12031-016-0748-1

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