ArticleAntioxidants (Basel, Switzerland)2020
The Circadian Hormone Melatonin Inhibits Morphine-Induced Tolerance and Inflammation via the Activation of Antioxidative Enzymes.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis.Journal of oral & facial pain and headache · 2022Pooled it
- Melatonin as an Integrative Adjunct in Multimodal Analgesia: Linking Circadian Regulation, Anti-Inflammatory Modulation, and Opioid-Sparing Mechanisms.International journal of molecular sciences · 2026Review
- Disrupted circadian rhythms and opioid-mediated adverse effects: Bidirectional relationship and putative mechanisms.Journal of neuroendocrinology · 2025Review
- Circadian Light Manipulation and Melatonin Supplementation Enhance Morphine Antinociception in a Neuropathic Pain Rat Model.International journal of molecular sciences · 2025Article
- Comparative Analysis of Melatonin and Polydeoxyribonucleotide: Possible Benefits of Co-Treatment Effects and Potential Synergistic Applicability.International journal of molecular sciences · 2025Review
- Review
- The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Melatonin Attenuates PFOS-Induced Reproductive Toxicity of Pregnant Mice due to Placental Damage Via Antioxidant, Anti-Aging and Anti-Inflammatory Pathways.Birth defects research · 2024Article
- Genome-Wide Analysis of Genetic Diversity and Selection Signatures in Zaobei Beef Cattle.Animals : an open access journal from MDPI · 2024Article
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Article
- Article
- Opioid-Use, COVID-19 Infection, and Their Neurological Implications.Frontiers in neurology · 2022Review
- Molecular Mechanism of Neuroprotective Effect of Melatonin on Morphine Addiction and Analgesic Tolerance: an Update.Molecular neurobiology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Opioids are commonly prescribed for clinical pain management; however, dose-escalation, tolerance, dependence, and addiction limit their usability for long-term chronic pain. The associated poor sleep pattern alters the circadian neurobiology, and further compromises the pain management. Here, we aim to determine the correlation between constant light exposure and morphine tolerance and explore the potential of melatonin as an adjuvant of morphine for neuropathic pain treatment.
methodsWistar rats were preconditioned under constant light (LL) or a regular light/dark (LD) cycle before neuropathic pain induction by chronic constriction injury. An intrathecal (i.t.) osmotic pump was used for continued drug delivery to induce morphine tolerance. Pain assessments, including the plantar test, static weight-bearing symmetry, and tail-flick latency, were used to determine the impact of the light disruption or exogenous melatonin on the morphine tolerance progression.
resultsconstant light exposure significantly aggravates morphine tolerance in neuropathic rats. Continued infusion of low-dose melatonin (3 μg/h) attenuated morphine tolerance in both neuropathic and naïve rats. This protective effect was independent of melatonin receptors, as shown by the neutral effect of melatonin receptors inhibitors. The transcriptional profiling demonstrated a significant enhancement of proinflammatory and pain-related receptor genes in morphine-tolerant rats. In contrast, this transcriptional pattern was abolished by melatonin coinfusion along with the upregulation of the
conclusionDysregulated circadian light exposure significantly compromises the efficacy of morphine's antinociceptive effect, while the cotreatment with melatonin attenuates morphine tolerance/hyperalgesia development. Our results suggest the potential of melatonin as an adjuvant of morphine in clinical pain management, particularly in patients who need long-term opioid treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.