Dexmedetomidine alleviates the labor pain by inhibiting the activation of MAPK/ERK signaling pathway due to reduced BDNF expression in rats
Objective:To investigate the effect and mechanism of different doses of dexmedetomidine(Dex)on labor pain in rats through the brain-derived neurotrophic factor(BDNF)/mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:A rat pregnancy model was established.The experimental animals were randomly divided into four groups.The rats in the control group underwent natural childbirth without any treatment;the three Dex groups,where rats were intravenously injected with 50,100,and 200 μg/kg Dex during the initiation of labor until the birth of the last pup.Immunohistochemistry was used to detect the BDNF expression in rat cortical parietal lobe of the brain and endometrial tissue.The tail immersion assay was used to determine the pain threshold and Richmond agitation-sedation scale scores during rat labor.The expression levels of rapidly accelerated fibrosarcoma(Raf),ERK,cAMP response element binding protein(CREB)and dynorphin(DYN)were detected by qRT-PCR and Western blotting in rat cortical parietal lobe of the brain and endometrial tissue.Results:The expression level of BDNF protein in rat cortical parietal lobe of the brain and endometrial tissue was significantly decreased by Dex in a dose-dependent manner.With the increase of Dex dose,intravenous injection of Dex significantly increased the pain threshold of laboring rats and decreased the Richmond agitation and sedation scores.Compared with the control group,the mRNA and protein expression levels of Raf,ERK and CREB in rat cortical parietal lobe of the brain and endometrium were significantly decreased after injection of Dex,while the mRNA and protein expression levels of DYN were significantly increased.Correlation analysis showed that BDNF expression was positively correlated with Raf,ERK and CREB expression in the cortical parietal lobe of the brain,but negatively correlated with the expression of DYN.BDNF expression had no correlation with Raf and ERK expression in endometrium,but was positively correlated with CREB expression and negatively correlated with DYN expression.Conclusion:Intravenous injection of Dex has an obvious inhibitory effect on labor pain in rats,and the mechanism may be closely related to the activation of MAPK/ERK signaling pathway through the action of BDNF.
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