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Updated: Jul 10, 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

Molecular interaction in the mouse PAG between NMDA and opioid receptors in morphine-induced acute thermal

Carla Ghelardini1, Nicoletta Galeotti, Elisa Vivoli

  • 1Department of Clinical and Preclinical Pharmacology, University of Florence, Italy.

Journal of Neurochemistry
|November 13, 2007
PubMed

Insights

Low dose morphine causes acute thermal hyperalgesia via micro-opioid receptor (microOR) activation in the periaqueductal gray. This involves NMDA receptor phosphorylation, mediated by protein kinase C, contributing to pain sensitivity.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Systemic low-dose morphine administration is known to induce acute thermal hyperalgesia.
  • This effect is mediated through micro-opioid receptor (microOR) stimulation and the inositol signaling pathway.

Purpose of the Study:

  • To identify the specific site of action for systemically administered low-dose morphine.
  • To elucidate the mechanism by which microOR activation by morphine influences the NMDA receptor in relation to acute thermal hyperalgesia.

Main Methods:

  • Utilized microOR antagonist CTOP, NMDA antagonist MK801, and protein kinase C inhibitor chelerythrine to block hyperalgesia.
  • Investigated the periaqueductal gray (PAG) as a potential site of action.
  • Assessed the phosphorylation of NMDA receptor subunits.

Main Results:

  • Acute thermal hyperalgesia was significantly blocked by CTOP, MK801, and chelerythrine in the periaqueductal gray.
  • Morphine's action appears localized to the PAG, a supraspinal site.
  • MicroOR stimulation by morphine increased the phosphorylation of a specific NMDA receptor subunit (subunit 1).
  • The phosphorylation of NMDA receptor subunit 1 correlated with the observed acute thermal hyperalgesia.

Conclusions:

  • The periaqueductal gray is identified as a key supraspinal site of action for low-dose morphine-induced acute thermal hyperalgesia.
  • MicroOR activation by morphine triggers NMDA receptor phosphorylation at the PAG.
  • Protein kinase C acts as a crucial link between microOR activation and the NMDA/glutamatergic system in mediating morphine-induced thermal hyperalgesia.

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