Related Experiment Video

Updated: Jun 8, 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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Morphine-induced hyperalgesia impacts small extracellular vesicle miRNA composition and function

Deepa Reddy1,2, Zhucheng Lin1,2, Sujay Ramanathan1,2

  • 1Department of Pharmacology & Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USA.

Biorxiv : the Preprint Server for Biology
|November 1, 2024
PubMed

Insights

Morphine treatment alters microRNAs in small extracellular vesicles (sEVs), potentially offering a new non-opioid pain therapy. These sEVs may help resolve inflammatory hypersensitivity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Opioid analgesics like morphine are common pain treatments.
  • Prolonged opioid use can paradoxically increase pain sensitivity (opioid-induced hyperalgesia).
  • The molecular mechanisms driving opioid-induced hyperalgesia remain incompletely understood.

Purpose of the Study:

  • To investigate molecular changes in serum-derived small extracellular vesicles (sEVs) following morphine administration.
  • To identify specific microRNAs (miRNAs) within sEVs that are dysregulated by morphine.
  • To assess the therapeutic potential of morphine-altered sEVs in pain management.

Main Methods:

  • Mice received morphine to induce hyperalgesia.
  • Serum sEVs were isolated and their miRNA composition analyzed.
  • Bioinformatic analysis predicted miRNA targets involved in pain pathways.
  • Creb mRNA regulation by specific miRNAs was experimentally confirmed.
  • Naïve mice received sEVs to assess behavioral effects.

Main Results:

  • Morphine treatment significantly altered the expression of 18 miRNAs in serum sEVs.
  • Several dysregulated miRNAs were predicted to target CREB (cyclic AMP response element binding protein).
  • miR-155 and miR-10a were confirmed to bind and repress Creb mRNA.
  • sEVs from morphine-treated mice accelerated the resolution of inflammatory hypersensitivity in naïve recipients.
  • No significant impact on basal pain thresholds, place preference, or locomotor sensitization was observed.

Conclusions:

  • Morphine alters serum sEV miRNA profiles, including those targeting CREB.
  • Serum sEVs from morphine-treated mice possess the capacity to mitigate inflammatory pain hypersensitivity.
  • sEVs represent a promising non-opioid therapeutic strategy for pain management.

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