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MiR-34a affects dexmedetomidine-inhibited chronic inflammatory visceral pain by targeting to HDAC2. | LitMetric

MiR-34a affects dexmedetomidine-inhibited chronic inflammatory visceral pain by targeting to HDAC2.

BMC Anesthesiol

Department of Anesthesiology, Weihai Central Hospital, No.3, West Mt. East Road, Wendeng District, Weihai City, 264400, Shandong, China.

Published: July 2019

AI Article Synopsis

Article Abstract

Background: Dexmedetomidine (DEX) has been used as an anesthetic for decades. The present investigation aimed to elucidate the analgesic impact of DEX on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced chronic inflammatory visceral pain (CIVP) in rats.

Methods: TNBS with or without DEX to Male Sprague-Dawley SD rats were randomly divided into four groups: normal, CIVP, DEX, and vehicle. Pain behaviors were assessed and the abdominal withdrawal reflex, mechanical withdrawal threshold, and thermal withdrawal latency were recorded. Quantitative polymerase chain reaction data showed increased expressions of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in the spinal cord tissues of rats.

Results: RNA microarray and quantitative polymerase chain reaction results indicated that miR-34a was downregulated by TNBS induction, but it was upregulated by DEX administration. Further studies showed that transfection of adenovirus-miR-34a inhibitor reversed the effect of DEX on the pain behaviors and spinal-cord pro-inflammatory-cytokine generation in CIVP rats. Additionally, we found that miR-34a targeted the 3'-UTR of the HDAC2 gene, as evinced by the increased HDAC2 expression in the CIVP and DEX + miR-34a inhibitor groups, and decreased HDAC2 signaling in the DEX group. Moreover, knock-down of HDAC2 restored DEX-attenuated pain behaviors and reduced pro-inflammatory cytokine production.

Conclusions: DEX thus exhibited an analgesic effect on CIVP rats through the miR-34a-mediated HDAC2 pathway and suppressed visceral hypersensitivity.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642536PMC
http://dx.doi.org/10.1186/s12871-019-0801-zDOI Listing

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