Related Experiment Video
Updated: Jun 30, 2026
07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Maresin1 mitigates morphine analgesic tolerance via the Lgr6 pathway
Xinyi Tian1, Jishi Ye2, Chenxi Shen1
1Department of Anesthesia, Critical Care and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of Pediatric Anesthesiology (Wenzhou Medical University), Ministry of Education, Wenzhou, China; Precision Anesthesiology Key Laboratory of Zhejiang Province, Wenzhou Medical University, Wenzhou, China.
Progress in Neurobiology
|April 9, 2026
Summary
Chronic morphine use lowers maresin1 levels, contributing to pain relief tolerance. Supplementing maresin1 (a specialized pro-resolving mediator) can restore morphine
Area of Science:
- Neuroscience
- Pharmacology
- Pain Management
Background:
- Repeated morphine administration causes analgesic tolerance, diminishing pain relief and increasing overdose risks.
- The role of specialized pro-resolving mediators (SPMs) and their interaction with mu-opioid receptors in morphine tolerance is not fully understood.
Purpose of the Study:
- To investigate the changes in endogenous maresin1 levels during chronic morphine exposure.
- To determine the role of maresin1 in modulating mu-opioid receptor function and analgesic tolerance.
- To explore the potential of maresin1 as a therapeutic target for improving opioid effectiveness.
Main Methods:
- Assessed maresin1 levels in mice and correlated them with morphine dosage in tolerant patients.
- Administered maresin1 systemically, intrathecally, and intracerebroventricularly to evaluate its effect on morphine tolerance.
- Investigated Lgr6 expression in dorsal root ganglia (DRG) of morphine-tolerant mice and utilized AAV injection to modulate Lgr6 expression.
- Examined the mechanism of maresin1 action, focusing on beta-arrestin2 recruitment and mu-opioid receptor internalization.
Main Results:
- Chronic morphine exposure significantly reduced maresin1 levels in mice.
- Systemic and intrathecal maresin1 administration alleviated morphine-induced analgesic tolerance.
- Lgr6 expression decreased in the DRG of morphine-tolerant mice, and its reduction negated maresin1's protective effects.
- Maresin1 was found to prevent beta-arrestin2 recruitment and mu-opioid receptor internalization, thereby preserving morphine's analgesic efficacy.
Conclusions:
- Maresin1 plays a crucial role in modulating morphine tolerance.
- Restoring maresin1 levels or enhancing its signaling may represent a novel strategy to counteract opioid tolerance and improve pain management.
- Targeting maresin1 offers a promising therapeutic avenue to enhance the effectiveness of morphine and reduce associated risks.
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