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Updated: Dec 29, 2025

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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Blood-borne and brain-derived microparticles in morphine-induced anti-nociceptive tolerance

Deepa Ruhela1, Veena M Bhopale1, Ming Yang1

  • 1Department of Emergency Medicine, United States.

Brain, Behavior, and Immunity
|February 1, 2020
PubMed

Insights

Morphine tolerance increases blood microparticles (MPs), particularly those from neutrophils, which are crucial for this effect. Similar MP elevations are seen in patients with opioid use disorder.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Opioid analgesics like morphine can lead to the development of anti-nociceptive tolerance, a reduced response to pain relief with repeated use.
  • The underlying mechanisms of morphine tolerance are not fully understood, but involve complex cellular and molecular changes.

Purpose of the Study:

  • To investigate the role of microparticles (MPs) in the development of morphine-induced anti-nociceptive tolerance.
  • To identify the cellular origins and key molecular components of MPs involved in tolerance.

Main Methods:

  • Morphine was administered repetitively to mice to induce anti-nociceptive tolerance.
  • Blood and lymph samples were analyzed for microparticle levels and cellular markers.
  • Interventions included IL-1β antagonist, MP-lysing agents, methylnaltrexone, and neutropenia induction.

Main Results:

  • Repetitive morphine administration significantly increased blood-borne MPs (8-fold) and MPs in cervical lymph nodes (10-fold).
  • MPs expressed proteins from neutrophils, microglia, astrocytes, neurons, and oligodendrocytes, with a 68-fold increase in Interleukin (IL)-1β content.
  • Inhibiting IL-1β, lysing MPs, or inducing neutropenia abrogated MP elevations and prevented tolerance development.

Conclusions:

  • Neutrophil-derived MPs, particularly those containing IL-1β, are essential for morphine-induced anti-nociceptive tolerance.
  • These findings suggest a novel mechanism involving MPs in opioid tolerance.
  • Similar MP elevations observed in patients with opioid use disorder warrant further investigation.
Keywords:
Interleukin-1βMethylnaltrexoneMicrogliaNeutrophilOpioidTolerance

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