ArticleMolecular pain
Clinical opioids differentially induce co-internalization of μ- and δ-opioid receptors.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The trial behind it
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Single-molecule characterization of opioid receptor heterodimers reveals soluble µ-δ dimer blocker peptide alleviates morphine tolerance.Nature communications · 2025Article
- Persistent Transcriptome Alterations in Zebrafish Embryos After Discontinued Opioid Exposure.International journal of molecular sciences · 2025Article
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Met-enkephalin modulates the stress responses of plasma concentrations of corticosterone, delta opioid receptor binding, pro-enkephalin expression, and processing in chickens.Frontiers in physiology · 2025Article
- Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.Molecular brain · 2019Article
- Mu-opioid Receptor (MOR) Biased Agonists Induce Biphasic Dose-dependent Hyperalgesia and Analgesia, and Hyperalgesic Priming in the Rat.Neuroscience · 2018Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Opioid receptors play an important role in mediating the spinal analgesia. The μ-opioid receptor is the major target of opioid drugs widely used in clinics. However, the regulatory mechanisms of analgesic effect and tolerance for clinical μ-opioid receptor-targeting opioids remain to be fully investigated. Previous studies showed the interaction of δ-opioid receptor with μ-opioid receptor to form the μ-opioid receptor/δ-opioid receptor heteromers that could be processed in the degradation pathway after δ-opioid receptor agonist treatment. Here, we showed that clinical μ-opioid receptor-targeting opioids, morphine, fentanyl, and methadone, but not tramadol, caused μ-opioid receptor co-internalization with δ-opioid receptors in both transfected human embryonic kidney 293 cells and primary sensory neurons. Prolonged treatment of morphine led to μ-opioid receptor co-degradation with δ-opioid receptors. Furthermore, fentanyl and methadone, but not tramadol, induced the drug tolerance similar to morphine. Thus, the clinical μ-opioid receptor-targeting opioids including morphine, fentanyl, and methadone induce μ-opioid receptor co-internalization with δ-opioid receptors, which may be involved in the analgesic tolerance of these opioids.
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