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Updated: Mar 4, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
07:23

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities

Published on: July 29, 2014

34.2K

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

Jian Wang1, Wei Xu1, Jiali Shao1

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

Oncotarget
|April 21, 2017
PubMed

Insights

MicroRNA-219-5p (miR-219) alleviates morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Restoring miR-219 levels may offer a novel strategy for managing pain and reducing tolerance to morphine.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Morphine tolerance presents a significant challenge in clinical pain management.
  • MicroRNAs (miRNAs) are increasingly recognized for their regulatory roles in morphine tolerance development.
  • miR-219-5p is implicated in central pain sensitization by targeting CaMKIIγ and activating NMDA receptors.

Purpose of the Study:

  • To investigate the role of miR-219-5p in attenuating morphine tolerance.
  • To elucidate the molecular mechanism involving CaMKIIγ and NMDA receptors.

Main Methods:

  • Chronic morphine treatment in vivo and in vitro models.
  • Lentiviral vectors for miR-219-5p overexpression.
  • Quantitative analysis of miR-219-5p, CaMKIIγ, and NMDA receptor subunit 1 (NR1) expression.

Main Results:

  • Chronic morphine treatment significantly decreased miR-219-5p expression.
  • Overexpression of miR-219-5p prevented morphine tolerance development.
  • miR-219-5p overexpression downregulated CaMKIIγ and NR1 expression, inhibiting the CaMKII/NMDA pathway.

Conclusions:

  • miR-219-5p plays a critical role in alleviating morphine tolerance.
  • Inhibition of the CaMKII/NMDA receptor pathway by miR-219-5p is the underlying mechanism.
  • Overexpression of miR-219-5p represents a potential therapeutic strategy for morphine tolerance.
Keywords:
CaMKIIγNMDAmicroRNAmorphine tolerance

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