ArticleJournal of molecular cell biology2019
Morphine induces dysfunction of PINK1/Parkin-mediated mitophagy in spinal cord neurons implying involvement in antinociceptive tolerance.
Article in Journal of molecular cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Photobiomodulation repairs the blood-spinal cord barrier in a mouse model of spinal cord injury.Neural regeneration research · 2026Article
- 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
- Pharmacological evaluation of physcion as a TRPV1 inhibitor with multimodal analgesic efficacy in experimental pain models.Biological research · 2025Article
- HIV-1 Tat Impairment of Mitochondrial Respiration via Complexes I and II Can Be Ameliorated by Allopregnanolone in Opioid-Exposed or Opioid-Naïve Cells and Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies.Neurochemical research · 2025Review
- Cordycepin ameliorates morphine tolerance by inhibiting spinal cord ferroptosis and inflammation via targeting SIRT1.International journal of medical sciences · 2025Article
- Morphine induces HADHA succinylation, while HADHA desuccinylation alleviates morphine tolerance by influencing autophagy.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Article
- Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.Current neuropharmacology · 2024Review
- Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.Neurochemical research · 2023Article
- Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances.Journal of translational medicine · 2023Review
- Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway.Neural regeneration research · 2023Article
- Mitophagy and reactive oxygen species interplay in Parkinson's disease.NPJ Parkinson's disease · 2022Review
- Morphine Prevents Ischemia/Reperfusion-Induced Myocardial Mitochondrial Damage by Activating δ-opioid Receptor/EGFR/ROS Pathway.Cardiovascular drugs and therapy · 2022Article
- Morphine-induced modulation of Nrf2-antioxidant response element signaling pathway in primary human brain microvascular endothelial cells.Scientific reports · 2022Article
- Fighting metallodrug resistance through alteration of drug metabolism and blockage of autophagic flux by mitochondria-targeting AIEgens.Chemical science · 2022Article
- Effect of PINK1 and Parkin gene silencing on sodium arsenite-induced mitophagy in normal rat liver cells (BRL-3A).Toxicology research · 2022Article
- Molecular Mechanism of Neuroprotective Effect of Melatonin on Morphine Addiction and Analgesic Tolerance: an Update.Molecular neurobiology · 2021Review
- Mitochondrial dysfunction in fibrotic diseases.Cell death discovery · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of opioid-induced analgesic tolerance is a clinical challenge in long-term use for managing chronic pain. The mechanisms of morphine tolerance are poorly understood. Mitochondria-derived reactive oxygen species (ROS) is a crucial signal inducing analgesic tolerance and pain. Chronic administration of morphine leads to robust ROS production and accumulation of damaged mitochondria, which are immediately removed by mitophagy. Here, we show that morphine inhibits mitochondria damage-induced accumulation of PTEN-induced putative kinase 1 (PINK1) in neurons. It interrupts the recruitment of Parkin to the impaired mitochondria and inhibits the ubiquitination of mitochondrial proteins catalyzed by Parkin. Consequently, morphine suppresses the recognition of autophagosomes to the damaged mitochondria mediated by LC3 and sequestosome-1 (SQSTM1/p62). Thus, morphine inhibits autophagy flux and leads to the accumulation of SQSTM1/p62. Finally, the impaired mitochondria cannot be delivered to lysosomes for degradation and ultimately induces robust ROS production and morphine tolerance. Our findings suggest that the dysfunction of mitophagy is involved in morphine tolerance. The deficiency of PINK1/Parkin-mediated clearance of damaged mitochondria is crucial for the generation of excessive ROS and important to the development of analgesic tolerance. These findings suggest that the compounds capable of stabilizing PINK1 or restoring mitophagy may be utilized to prevent or reduce opioid tolerance during chronic pain management.
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