Research Papers:

miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats

Jian Wang, Wei Xu, Jiali Shao, Zhenghua He, Zhuofeng Ding, Jiangju Huang, Qulian Guo and Wangyuan Zou _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:28203-28214. https://doi.org/10.18632/oncotarget.15997

Metrics: PDF 1406 views  |   HTML 1954 views  |   ?  


Jian Wang1, Wei Xu1, Jiali Shao1, Zhenghua He1, Zhuofeng Ding1, Jiangju Huang1, Qulian Guo1, Wangyuan Zou1

1Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China

Correspondence to:

Wangyuan Zou, email: wangyuanzou@hotmail.com

Keywords: morphine tolerance, microRNA, CaMKIIγ, NMDA

Received: August 31, 2016     Accepted: February 27, 2017     Published: March 08, 2017


Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment. Overexpression of miR-219-5p by lentivirus injection prevents the development of morphine tolerance. CaMKIIγ, the target gene of miR-219-5p was downregulated by overexpression of miR-219-5p both in vivo and in vitro. Furthermore, we found that lentiviral-mediated miR-219-5p decreased the expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine tolerance.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15997