Upregulation of MiR-375 Level Ameliorates Morphine Analgesic Tolerance in Mouse Dorsal Root Ganglia by Inhibiting the JAK2/STAT3 Pathway
Overview
Authors
Affiliations
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.
Bioinformatic Analysis from a Descriptive Profile of miRNAs in Chronic Migraine.
Tovar-Cuevas A, Rosales Gomez R, Martin-Marquez B, Pena Duenas N, Sandoval-Garcia F, Guzman Ornelas M Int J Mol Sci. 2024; 25(19).
PMID: 39408819 PMC: 11477213. DOI: 10.3390/ijms251910491.
Targeting the JAK2/STAT3 signaling pathway for chronic pain.
Dai X, Liu L, Song F, Gao S, Wu J, Li D Aging Dis. 2023; 15(1):186-200.
PMID: 37307838 PMC: 10796104. DOI: 10.14336/AD.2023.0515.
Noncoding RNAs: Novel Targets for Opioid Tolerance.
Deng M, Zou W Curr Neuropharmacol. 2022; 21(5):1202-1213.
PMID: 36453497 PMC: 10286586. DOI: 10.2174/1570159X21666221129122932.
Liu X, Geng J, Bu H, Ma J, Ai Y RSC Adv. 2022; 9(70):40895-40902.
PMID: 35540064 PMC: 9076454. DOI: 10.1039/c9ra06264e.
Lu F, Zhang N, Ye T, Zhao H, Pang M, Liu S RSC Adv. 2022; 9(31):17791-17800.
PMID: 35520561 PMC: 9064686. DOI: 10.1039/c8ra10443c.