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ABSTRACT: Background
Morphine is widely used in clinical practice for a class of analgesic drugs, long-term use of morphine will cause the action of tolerance. MicroRNAs have been reported to be involved in morphine analgesic tolerance..Methods
Forty male SD rats were selected and randomly divided into 5 groups: the control group, morphine tolerance group, miR-365 mimic + morphine (miR-365 mimic) group, miR-365 inhibitor + morphine (miR-365 inhibitor) group and miR-365 negative control (NC) + morphine (miR-365 NC) group. After the administration of morphine at 0 d, 1 d, 3 d, 5 d and 7 d, behavioral testing was performed. A dual luciferase reporter gene assay was performed to confirm the relationship between miR-365 and β-arrestin2, RT-qPCR was used to detect miR-365, β-arrestin2, ERK and CREB mRNA expressions, western blotting was used to evaluate the protein expressions of β-arrestin2, ERK, p-ERK, CREB and p-CREB, ELISA was used to detect the contents of IL-1β, TNF-α and IL-18, while immunofluorescence staining was used to measure the GFAP expression. Intrathecal injection of mir365 significantly increased the maximal possible analgesic effect (%MPE) in morphine tolerant rats. β-arrestin2 was the target gene of miR-365.Results
The results obtained showed that when compared with the morphine tolerance group, there was an increase in miR-365 expression and a decrease in the β-arrestin2, ERK, CREB protein expressions, contents of IL-1β, TNF-α, IL-18 and GFAP expression in the miR-365 mimic group, while the miR-365 inhibitor group displayed an opposite trend.Conclusions
The results of this experiment suggest that by targeting β-arrestin2 to reduce the contents of IL-1β, TNF-α and IL-18 and by inhibiting the activation of ERK/CREB signaling pathway, miR-365 could lower morphine analgesic tolerance.
SUBMITTER: Wu XP
PROVIDER: S-EPMC5802062 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature

Wu Xian-Ping XP She Rui-Xuan RX Yang Yan-Ping YP Xing Zu-Min ZM Chen Han-Wen HW Zhang Yi-Wen YW
Journal of biomedical science 20180207 1
<h4>Background</h4>Morphine is widely used in clinical practice for a class of analgesic drugs, long-term use of morphine will cause the action of tolerance. MicroRNAs have been reported to be involved in morphine analgesic tolerance..<h4>Methods</h4>Forty male SD rats were selected and randomly divided into 5 groups: the control group, morphine tolerance group, miR-365 mimic + morphine (miR-365 mimic) group, miR-365 inhibitor + morphine (miR-365 inhibitor) group and miR-365 negative control (NC ...[more]