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

BMC Anesthesiol. 2019 Jul 19;19(1):131. doi: 10.1186/s12871-019-0801-z.

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.

Keywords: CIVP; DEX; HDAC; Pain behaviors; miR-34a.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Chronic Pain / therapy
  • Cytokines / metabolism
  • Dexmedetomidine / pharmacology*
  • Down-Regulation
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / metabolism*
  • Hypnotics and Sedatives / pharmacology
  • Male
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Pain Threshold
  • Polymerase Chain Reaction
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reflex
  • Spinal Cord / metabolism
  • Trinitrobenzenesulfonic Acid / adverse effects
  • Up-Regulation
  • Visceral Pain / chemically induced
  • Visceral Pain / therapy*

Substances

  • 3' Untranslated Regions
  • Cytokines
  • Hypnotics and Sedatives
  • MIRN34 microRNA, rat
  • MicroRNAs
  • Dexmedetomidine
  • Trinitrobenzenesulfonic Acid
  • Hdac2 protein, rat
  • Histone Deacetylase 2