ArticleRedox biology2020
Melatonin alleviates morphine analgesic tolerance in mice by decreasing NLRP3 inflammasome activation.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 79 citations in OpenAlex.
- TRPV1 channel antagonist capsazepine alleviates morphine tolerance and morphine-induced neurotoxicity by preventing mitochondrial damage and apoptosis: an in vivo and in vitro study.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Preclinical Assessment of a Metformin-Melatonin Combination: Antinociceptive Synergism.Pharmaceutics · 2025Article
- Circadian Light Manipulation and Melatonin Supplementation Enhance Morphine Antinociception in a Neuropathic Pain Rat Model.International journal of molecular sciences · 2025Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- Targeting the self-amplifying loop between ATF6 and SNAI1 to inhibit epithelial‒mesenchymal transition in fibrotic lesions.Theranostics · 2025Article
- Article
- Involvement of Melatonin, Oxidative Stress, and Inflammation in the Protective Mechanism of the Carotid Artery over the Torpor-Arousal Cycle of Ground Squirrels.International journal of molecular sciences · 2024Article
- Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells.Journal of ovarian research · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.Cellular & molecular immunology · 2024Article
- Calcitonin gene-related peptide attenuated discogenic low back pain in rats possibly via inhibiting microglia activation.Heliyon · 2024Article
- Zingerone Alleviates Morphine Tolerance and Dependence in Mice by Reducing Oxidative Stress-Mediated NLRP3 Inflammasome Activation.Neurochemical research · 2024Article
- Effect of NLRP3 inflammasome induced astrocyte phenotype alteration in morphine tolerance.Frontiers in pharmacology · 2024Article
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.Neurochemical research · 2023Article
- Article
- Cross-sectional analysis of potential risk factors of the pineal gland calcification.BMC endocrine disorders · 2023Article
- Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease.International journal of nanomedicine · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphine is frequently used for pain relief, but long-term morphine therapy in patients with chronic pain results in analgesic tolerance and hyperalgesia. There are no effective therapeutic treatments that limit these detrimental side effects. We found pretreatment with melatonin could decrease morphine-induced analgesic tolerance. There was a significant activation of the NLRP3 inflammasome in the prefrontal cortex and the peripheral blood of morphine-treated mice compared to control animals, which could be blocked by melatonin. The inflammasome activation induced by morphine was mediated by the microglia. SiRNA knockdown or pharmacological inhibition of the NLRP3 abolished the morphine-induced inflammasome activation. Co-administration of melatonin and low-dose morphine had better analgesia effects in the murine models of pain and led to a lower NLRP3 inflammasome activity in brain tissues. Mice deficient for Nlrp3 had a higher nociceptive threshold and were less sensitive to develop morphine-induced analgesic tolerance and acetic acid-induced pain relative to wild-type animals. Concordantly, we observed a significantly elevated level of serum IL-1β, which indicates an increase of NLRP3 inflammasome activity associated with the reduced level of serum melatonin, in heroin-addicted patients relative to healthy individuals. Our results provide a solid basis for conducting a clinical trial with the co-administration of melatonin and morphine for the relief of severe pain.
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