ArticlePurinergic signalling2016
Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia.
Article in Purinergic signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.Journal of psychoactive drugsTrial
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Kratom (Molecules (Basel, Switzerland) · 2026Article
- Transcutaneous Electrical Acupoint Stimulation for Opioid Tolerance in Hepatocellular Carcinoma and Proteomics Analysis: A Randomized Controlled Trial Protocol.Journal of pain research · 2026Article
- Pharmacokinetic analysis of morphine-3-glucuronide after acute morphine intravenous bolus administration to rats with traumatic brain injury.The Journal of pharmacology and experimental therapeutics · 2025Article
- Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review.Biomedicines · 2025Review
- The therapeutic potential of phytochemicals in morphine tolerance: targeting microglia-mediated neuroinflammation.Frontiers in pharmacology · 2025Review
- Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex.Translational psychiatry · 2024Article
- The Inflammation/NF-κB and BDNF/TrkB/CREB Pathways in the Cerebellum Are Implicated in the Changes in Spatial Working Memory After Both Morphine Dependence and Withdrawal in Rat.Molecular neurobiology · 2024Article
- Fentanyl Overdose Causes Prolonged Cardiopulmonary Dysregulation in Male SKH1 Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the Dorsolateral Prefrontal Cortex.bioRxiv : the preprint server for biology · 2024Article
- Fentanyl enhances immune cell response through TLR4/MD-2 complex.Frontiers in pharmacology · 2024Article
- Microglia in morphine tolerance: cellular and molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2024Review
- Prenatal alcohol exposure promotes NLRP3 inflammasome-dependent immune actions following morphine treatment and paradoxically prolongs nerve injury-induced pathological pain in female mice.Alcohol, clinical & experimental research · 2023Article
- Microglial inflammation modulates opioid analgesic tolerance.Journal of neuroscience research · 2023Review
- Transcriptional and epigenetic regulation of microglia in substance use disorders.Molecular and cellular neurosciences · 2023Review
- The Crosstalk between the Blood-Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia.Current issues in molecular biology · 2022Review
- Stress- and drug-induced neuroimmune signaling as a therapeutic target for comorbid anxiety and substance use disorders.Pharmacology & therapeutics · 2022Review
- Endogenous opioid systems alterations in pain and opioid use disorder.Frontiers in systems neuroscience · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphine creates a neuroinflammatory response and enhances release of the proinflammatory cytokines like interleukin-1β (IL-1β), which compromises morphine analgesia as well as induces morphine tolerance. In this study, we attempted to investigate the mechanisms of morphine induced IL-1β synthesis and release. Microglial cells were treated with morphine (100 μM) once daily for 3 days. Control groups underwent the same procedure but received sterile saline injection instead of morphine. Toll-like receptor 4 (TLR4) and P2X4 receptor (P2X4R) signaling were analyzed using Western blot; immunofluorescence was used to detect the signaling of CD68; real-time RT-PCR and ELISA kit was used to measure the messenger RNA and protein synthesis and release level of IL-1β. Morphine enhanced IL-1β synthesis and P2X4R protein expression. TLR4 were responsible for morphine-induced IL-1β synthesis, while morphine-induced IL-1β release was via P2X4R. Morphine-induced IL-1β release is mediated by endocytosis of TLR4. These results indicated that TLR4 and P2X4R pathways mediated IL-1β synthesis and release in microglia followed chronic morphine. TLR4 internalization is the main mechanism of morphine-induced microglia activation and IL-1β release.
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