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Updated: Jun 22, 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

Mechanisms underlying morphine analgesic tolerance and dependence

Hiroshi Ueda1, Mutsumi Ueda

  • 1Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ueda@nagasakiu.ac.jp

Frontiers in Bioscience (Landmark Edition)
|June 2, 2009
PubMed

Insights

Opioid tolerance involves cellular changes and neuronal circuit adaptations. This review highlights neuronal circuit plasticity, focusing on glutamate and NMDA receptor activity, as key to understanding opioid tolerance.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cellular Biology

Background:

  • Opioid tolerance mechanisms are complex, involving cellular adaptations like receptor desensitization.
  • Existing research primarily focuses on cellular mechanisms, potentially overlooking other contributing factors.
  • Opioid tolerance and dependence are not fully explained by cellular adaptation alone.

Purpose of the Study:

  • To review the role of neuronal circuit plasticity in opioid tolerance.
  • To explore the involvement of glutamate and NMDA receptor pathways in anti-opioid mechanisms.
  • To introduce novel methods for identifying brain regions associated with opioid tolerance.

Main Methods:

  • Literature review focusing on cellular and neuronal circuit plasticity.
  • Analysis of receptor up-regulation and down-regulation of transporters.
  • Introduction of in vivo electroporation for brain loci identification.

Main Results:

  • Neuronal circuit plasticity, specifically enhanced synaptic activity involving glutamate and NMDA receptors, contributes to opioid tolerance.
  • Up-regulation of D-serine production and down-regulation of glutamate transporters create anti-opioid effects.
  • Altered expression of molecules in neuron-glial networks may augment this anti-opioid system.

Conclusions:

  • Neuronal circuit plasticity is a critical, underemphasized component of opioid tolerance.
  • The interplay between glutamate, NMDA receptors, and neuron-glial networks forms an anti-opioid system.
  • In vivo electroporation offers a promising approach to pinpoint brain regions involved in opioid tolerance and dependence.

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