Research Papers:
miR2195p targets CaMKIIγ to attenuate morphine tolerance in rats
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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: [email protected]
Keywords: morphine tolerance, microRNA, CaMKIIγ, NMDA
Received: August 31, 2016 Accepted: February 27, 2017 Published: March 08, 2017
ABSTRACT
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.