Upregulation of miR-375 level ameliorates morphine analgesic tolerance in mouse dorsal root ganglia by inhibiting the JAK2/STAT3 pathway

作者：Li, Haiqin; Tao, Rong; Wang, Jing; Xia, Lingjie^*

来源：Journal of Pain Research, 2017, 10: 1279-1287.

DOI：10.2147/JPR.S125264

• morphine tolerance
• miR-375
• JAK2
• BDNF

Several lines of evidence indicate that microRNAs (miRNAs) modulate tolerance to the analgesic effects of morphine via regulation of pain-related genes, making dysregulation of miRNA levels a clinical target for controlling opioid tolerance. However, the precise mechanisms by which miRNAs regulate opioid tolerance are unclear. In the present study, we noted that the miR-375 level was downregulated but the expression of Janus kinase 2 (JAK2) was upregulated in mouse dorsal root ganglia (DRG) following chronic morphine treatment. The miR-375 levels and JAK2 expression were correlated with the progression of morphine tolerance, and upregulation of miR-375 level could significantly hinder morphine tolerance. This was ameliorated by JAK2 knockdown. Prolonged morphine exposure induced the expression of brain-derived neurotrophic factor (BDNF) in a time-dependent manner in the DRG. This was regulated by the miR-375 and JAK2-signal transducer and activator of transcription 3 (STAT3) pathway, and inhibition of this pathway decreased BDNF production, and thus, attenuated morphine tolerance. More importantly, we found that miR-375 could target JAK2 and increase BDNF expression in a JAK2/STAT3 pathway-dependent manner.

• 出版日期2017
• 单位郑州大学; 河南省人民医院