PMID- 28603428
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 1178-7090 (Print)
IS  - 1178-7090 (Electronic)
IS  - 1178-7090 (Linking)
VI  - 10
DP  - 2017
TI  - Upregulation of miR-375 level ameliorates morphine analgesic tolerance in mouse 
      dorsal root ganglia by inhibiting the JAK2/STAT3 pathway.
PG  - 1279-1287
LID - 10.2147/JPR.S125264 [doi]
AB  - 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.
FAU - Li, Haiqin
AU  - Li H
AD  - Department of Clinical Pain, The People's Hospital of Henan Province, Zhengzhou, 
      People's Republic of China.
FAU - Tao, Rong
AU  - Tao R
AD  - Department of Clinical Pain, The People's Hospital of Henan Province, Zhengzhou, 
      People's Republic of China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Clinical Pain, The People's Hospital of Henan Province, Zhengzhou, 
      People's Republic of China.
FAU - Xia, Lingjie
AU  - Xia L
AD  - Department of Clinical Pain, The People's Hospital of Henan Province, Zhengzhou, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20170526
PL  - New Zealand
TA  - J Pain Res
JT  - Journal of pain research
JID - 101540514
PMC - PMC5457281
OTO - NOTNLM
OT  - BDNF
OT  - JAK2
OT  - miR-375
OT  - morphine tolerance
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2017/06/13 06:00
MHDA- 2017/06/13 06:01
PMCR- 2017/05/26
CRDT- 2017/06/13 06:00
PHST- 2017/06/13 06:00 [entrez]
PHST- 2017/06/13 06:00 [pubmed]
PHST- 2017/06/13 06:01 [medline]
PHST- 2017/05/26 00:00 [pmc-release]
AID - jpr-10-1279 [pii]
AID - 10.2147/JPR.S125264 [doi]
PST - epublish
SO  - J Pain Res. 2017 May 26;10:1279-1287. doi: 10.2147/JPR.S125264. eCollection 2017.