Retracted Article: Upregulation of MiR-26b Alleviates Morphine Tolerance by Inhibiting BDNF Wnt/β-catenin Pathway in Rats

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 May 11

PMID 35540064

Authors

Xing Liu

Jiefeng Geng

Huilian Bu

Junqi Ma

Yanqiu Ai

Affiliations

Soon will be listed here.

Abstract

: Morphine is a commonly used analgesic drug. However, long-term use of morphine will cause tolerance which limits its clinical application in pain treatment. MicroRNAs (miRNAs) have been reported to be involved in the morphine tolerance, but the underlying mechanism is still poorly understood. : Tail flick test was used to measure the maximum possible effect (MPE). Quantitative real-time PCR was employed to detect miR-26b, BDNF, and Wnt5a expression in rat dorsal root ganglia (DRG). Luciferase report assay was introduced to verify the binding relationship between miR-26b and Wnt5a. BDNF, Wnt5a and β-catenin protein level were tested by western blotting. : MiR-26b was down-regulated during the development of morphine tolerance while BDNF was upregulated. Overexpression of miR-26b or BDNF inhibition alleviated morphine tolerance. Wnt5a was directly targeted and inhibited by miR-26b binding to the 3'-UTR of Wnt5a. The Wnt/β-catenin pathway was active in morphine tolerant rats. Moreover, overexpression of Wnt5a could partially enhance miR-26 mimic-mediated morphine tolerance, while a Wnt5a inhibitor could attenuate the tolerance. : The present study demonstrated that miR-26b overexpression alleviated morphine tolerance by inhibiting BDNF the Wnt/β-catenin pathway in rats, highlighting a promising target for the treatment of morphine tolerance.

References

Acheson A, Conover J, Fandl J, DeChiara T, Russell M, Thadani A . A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995; 374(6521):450-3. DOI: 10.1038/374450a0. View

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

Mei H, Zhou M, Zhang X, Huang X, Wang Y, Wang P . Effects of on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain. Biosci Rep. 2017; 37(2). PMC: 5350600. DOI: 10.1042/BSR20160517. View

Bali K, Kuner R . Noncoding RNAs: key molecules in understanding and treating pain. Trends Mol Med. 2014; 20(8):437-48. PMC: 4123187. DOI: 10.1016/j.molmed.2014.05.006. View

Bhalala O, Srikanth M, Kessler J . The emerging roles of microRNAs in CNS injuries. Nat Rev Neurol. 2013; 9(6):328-39. PMC: 3755895. DOI: 10.1038/nrneurol.2013.67. View

Chang G, Chen L, Mao J . Opioid tolerance and hyperalgesia. Med Clin North Am. 2007; 91(2):199-211. DOI: 10.1016/j.mcna.2006.10.003. View

Bai G, Ambalavanar R, Wei D, Dessem D . Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain. Mol Pain. 2007; 3:15. PMC: 1896151. DOI: 10.1186/1744-8069-3-15. View

Obata K, Noguchi K . BDNF in sensory neurons and chronic pain. Neurosci Res. 2006; 55(1):1-10. DOI: 10.1016/j.neures.2006.01.005. View

Rosenblum A, Marsch L, Joseph H, Portenoy R . Opioids and the treatment of chronic pain: controversies, current status, and future directions. Exp Clin Psychopharmacol. 2008; 16(5):405-16. PMC: 2711509. DOI: 10.1037/a0013628. View

10.

Wang J, Xu W, Zhong T, Song Z, Zou Y, Ding Z . miR-365 targets β-arrestin 2 to reverse morphine tolerance in rats. Sci Rep. 2016; 6:38285. PMC: 5138852. DOI: 10.1038/srep38285. View

11.

Huang E, Reichardt L . Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001; 24:677-736. PMC: 2758233. DOI: 10.1146/annurev.neuro.24.1.677. View

12.

Ni J, Gao Y, Gong S, Guo S, Hisamitsu T, Jiang X . Regulation of μ-opioid type 1 receptors by microRNA134 in dorsal root ganglion neurons following peripheral inflammation. Eur J Pain. 2012; 17(3):313-23. DOI: 10.1002/j.1532-2149.2012.00197.x. View

13.

McQuay H . Opioid use in chronic pain. Acta Anaesthesiol Scand. 1997; 41(1 Pt 2):175-83. DOI: 10.1111/j.1399-6576.1997.tb04634.x. View

14.

Harden R . Chronic pain and opiates: a call for moderation. Arch Phys Med Rehabil. 2008; 89(3 Suppl 1):S72-6. DOI: 10.1016/j.apmr.2007.12.013. View

15.

Wang Z, Wang L . Phosphorylation: a molecular switch in opioid tolerance. Life Sci. 2006; 79(18):1681-91. DOI: 10.1016/j.lfs.2006.05.023. View

16.

Wang Y, Liao J, Tang S, Shu J, Zhang W . HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway. J Mol Neurosci. 2017; 62(2):199-208. PMC: 6005692. DOI: 10.1007/s12031-017-0931-z. View

17.

Chao Y, Xie F, Li X, Guo R, Yang N, Zhang C . Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats. Neurochem Int. 2016; 97:91-8. DOI: 10.1016/j.neuint.2016.03.007. View

18.

Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C . BDNF as a pain modulator. Prog Neurobiol. 2008; 85(3):297-317. DOI: 10.1016/j.pneurobio.2008.04.004. View

19.

Gintzler A, Chakrabarti S . Opioid tolerance and the emergence of new opioid receptor-coupled signaling. Mol Neurobiol. 2001; 21(1-2):21-33. DOI: 10.1385/MN:21:1-2:021. View

20.

Hatami H, Oryan S, Semnanian S, Kazemi B, Bandepour M, Ahmadiani A . Alterations of BDNF and NT-3 genes expression in the nucleus paragigantocellularis during morphine dependency and withdrawal. Neuropeptides. 2007; 41(5):321-8. DOI: 10.1016/j.npep.2007.04.007. View