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MicroRNA-211-5p Enhances Analgesic Effect of Dexmedetomidine on Inflammatory Visceral Pain in Rats by Suppressing ERK Signaling

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Abstract

Dexmedetomidine (DEX) is a high-selectivity α2 adrenergic receptor agonist. The present study aimed to characterize the analgesic effects of DEX on TNBS-induced chronic inflammatory visceral pain (CIVP) in rats and to evaluate whether its antinociceptive effect is regulated by microRNAs (miRNAs) and the ERK pathway. TNBS with or without DEX was administered to 60 male Sprague-Dawley rats. These rats were randomly classified into four groups: control, TNBS, vehicle, and DEX groups. Pain behaviors were assessed by the abdominal withdrawal reflex (AWR), thermal withdrawal latency (TWL), and mechanical withdrawal threshold (MWT). qPCR, ELISA, and western blotting results showed increased serum IL-1β, TNF-α, and IL-6 levels. RNA microarray and qPCR results indicated that miR-211 was downregulated by CIVP induction but upregulated by DEX administration. ERK signaling was decreased in the TNBS+miR-211 group and increased in the DEX + miR-211 group, indicating that miR-211 targeted the 3′-UTR of the ERK gene. Moreover, ectopic expression of miR-211 in these two groups ameliorated pain behaviors and reduced proinflammatory cytokine production. Therefore, DEX exhibited an analgesic effect on CIVP in rats through a miR-211-mediated MEK/ERK/CREB pathway, suppressing visceral hypersensitivity.

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Funding

This work was supported by Beijing Science and Technology Commission Fund [Z171100000417035].

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Author notes

  1. Li Sun and Jinjun Zhou contributed equally to this work and should be considered as equal first coauthors.

Authors and Affiliations

  1. Department of Anesthesiology, The Seventh Medical Center of PLA General Hospital, Beijing, China

    Li Sun

  2. Department of Anesthesiology, Ezhou Women and Children Health Hospital, Ezhou, Hubei, China

    Jinjun Zhou

  3. Department of Anesthesiology, Affiliated Huxi Hospital of Jining Medical College, Shanxian Central Hospital, No.1, Wenhua Road, Shanxian County, Heze, 274300, Shandong, China

    Chaohui Sun

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  1. Li Sun
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  2. Jinjun Zhou
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  3. Chaohui Sun
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Correspondence to Chaohui Sun.

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Sun, L., Zhou, J. & Sun, C. MicroRNA-211-5p Enhances Analgesic Effect of Dexmedetomidine on Inflammatory Visceral Pain in Rats by Suppressing ERK Signaling. J Mol Neurosci 68, 19–28 (2019). https://doi.org/10.1007/s12031-019-01278-z

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  • DOI: https://doi.org/10.1007/s12031-019-01278-z

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