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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

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Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice

David Reiss1,2,3,4, Tando Maduna1,2,3,4,5, Hervé Maurin1,2,3,4

  • 1Translational Medicine and Neurogenetics Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.

Journal of Neuroscience Research
|April 8, 2020
PubMed

Insights

Targeting microglial mu opioid receptors (MOR) may offer new pain relief. Deleting MOR in microglia delayed tolerance and reduced side effects like hyperalgesia and dependence, suggesting a novel therapeutic approach.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Immunology

Background:

  • Opioid analgesics are effective but cause adverse effects.
  • Neuroinflammation, particularly microglial activation, contributes to opioid side effects.
  • The role of the microglial mu opioid receptor (MOR) in these effects is unclear.

Purpose of the Study:

  • To investigate the role of microglial MOR in opioid analgesia, tolerance, hyperalgesia, and dependence.
  • To develop and utilize a novel conditional knockout (cKO) mouse model to delete MOR specifically in microglia.

Main Methods:

  • Generated a conditional knockout (cKO) mouse line with MOR deleted in microglia.
  • Assessed morphine analgesic tolerance using the hot plate assay.
  • Measured opioid-induced hyperalgesia (OIH) via tail immersion assay.
  • Evaluated physical dependence using naloxone-induced withdrawal.

Main Results:

  • Morphine analgesic tolerance was delayed in both sexes of cKO mice.
  • OIH was abolished in male cKO mice.
  • Morphine physical dependence was attenuated in female cKO mice.
  • Demonstrated a sex-dependent role for microglial MOR.

Conclusions:

  • Microglial MOR plays a significant, sex-dependent role in morphine's effects.
  • Blocking microglial MOR may be a therapeutic strategy for opioid analgesia.
  • This approach could mitigate adverse effects associated with opioid use.
Keywords:
conditional knockoutmicrogliamorphineopioid receptoropioid-induced hyperalgesiatolerancewithdrawal

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