ArticlePloS one2016
Inhibition of Spinal Oxidative Stress by Bergamot Polyphenolic Fraction Attenuates the Development of Morphine Induced Tolerance and Hyperalgesia in Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
The trial behind it
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Pooled it
- Modulation of Mu-Opioid Receptor Expression and Functional Impairment of Natural Killer Cells in Neuropathic Pain: Implications for Biomarker Discovery and Personalized Therapies.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Betulin-NLC-hydrogel for the Treatment of Psoriasis-like Skin Inflammation: Optimization, Characterisation, andCurrent drug delivery · 2025Article
- Multiple Aspects of Irritable Bowel Syndrome and the Role of the Immune System: An Overview of Systematic Reviews with a Focus on Polyphenols.International journal of molecular sciences · 2024Review
- Exploring the Role of Bergamot Polyphenols in Alleviating Morphine-Induced Hyperalgesia and Tolerance through Modulation of Mitochondrial SIRT3.Nutrients · 2024Article
- Design of Mixed Medicinal Plants, Rich in Polyphenols, Vitamins B, and Palmitoylethanolamide-Based Supplement to Help Reduce Nerve Pain: A Preclinical Study.International journal of molecular sciences · 2024Article
- Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats.Antioxidants (Basel, Switzerland) · 2023Article
- Mechanisms underlying the anti-aging activity of bergamot (Frontiers in physiology · 2023Article
- Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.Molecules (Basel, Switzerland) · 2022Article
- A Systematic Review and Meta-Analysis on the Role of Nutraceuticals in the Management of Neuropathic Pain in In Vivo Studies.Antioxidants (Basel, Switzerland) · 2022Review
- Pain in Hemophilia: Unexplored Role of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
- The Employment of GeneraNutrients · 2022Review
- Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury.Oxidative medicine and cellular longevity · 2022Review
- The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Review
- Mild Cognitive Impairment and Mild Dementia: The Role ofPharmaceuticals (Basel, Switzerland) · 2021Review
- Endothelial Dysfunction and Extra-Articular Neurological Manifestations in Rheumatoid Arthritis.Biomolecules · 2021Review
- The Role of Nutraceuticals in Osteoarthritis Prevention and Treatment: Focus on n-3 PUFAs.Oxidative medicine and cellular longevity · 2021Review
- Protective Effect of Antioxidants in Nitric Oxide/COX-2 Interaction during Inflammatory Pain: The Role of Nitration.Antioxidants (Basel, Switzerland) · 2020Article
- Natural Antioxidant Control of Neuropathic Pain-Exploring the Role of Mitochondrial SIRT3 Pathway.Antioxidants (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrus Bergamia Risso, commonly known as Bergamot, is a fruit whose Essential Oil and Bergamot Polyphenolic Fraction have numerous medicinal properties. It is also an excellent antioxidant and in this study, for the first time, its potential effect on morphine induced tolerance in mice has been investigated. Our studies revealed that development of antinociceptive tolerance to repeated doses of morphine in mice is consistently associated with increased formation of superoxide, malondialdehyde and tyrosine-nitrated proteins in the dorsal horn of the spinal cord such as the enzyme glutamine synthase. Nitration of this protein is intimately linked to inactivation of its biological function and resulting increase of glutamate levels in the spinal cord. Administration of Bergamot Polyphenolic Fraction (5-50 mg/kg) attenuated tolerance development. This effect was accompanied by reduction of superoxide and malondialdehyde production, prevention of GS nitration, re-establishment of its activity and of glutamate levels. Our studies confirmed the main role of free radicals during the cascade of events induced by prolonged morphine treatment and the co-administration of natural derivatives antioxidant such as Bergamot Polyphenolic Fraction can be an important therapeutic approach to restore opioids analgesic efficacy.
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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.