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Updated: Jun 8, 2025
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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
Summary
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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