ReviewPeptides2019
Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.
Review in Peptides, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 102 citations in OpenAlex.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- The effect of neuroimmune signalling on drug addiction.Frontiers in pharmacology · 2026Review
- BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.Frontiers in neuroscience · 2026Article
- Intraoperative pain management for patients undergoing medication-assisted rehabilitation: a scoping review.BMC anesthesiology · 2025Article
- TLRs/PI3K/AKT1B Signaling Pathway Is Involved in Modulation of Neuroinflammation in the Rat Hippocampus by Alpha-pinene in Morphine-dependent and Withdrawing Rats.Neurochemical research · 2025Article
- Gender dependent modulation of opioid dependance genes and signaling pathways in HIV-1 Transgenic rats at morphine tolerance.Journal of neurovirology · 2025Article
- Pharmacological Perspective on the Neurobiology of PI3K-Akt-mTOR Signalling in Opioid Dependence.CNS & neurological disorders drug targets · 2025Review
- Neuroimmune modulatory effects of the NLRP3 inflammasome: the role of sex and living environment in brain affecting conditions.Frontiers in immunology · 2025Review
- Therapeutic Potential of Black Seed and Opium Poppy Oils in Mitigating Morphine Withdrawal Syndrome in an Animal Model.Addiction & health · 2025Article
- Single-Cell RNA Transcriptomics and Multi-omics Analyses Reveal the Clinical Effects of Acupuncture on Methadone Reduction.Research (Washington, D.C.) · 2025Article
- 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
- Article
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- The effect of cannabinoid type 2 receptor agonist on morphine tolerance.IBRO neuroscience reports · 2024Review
- The Effect of Prenatal and Neonatal Fluoride Exposure to Morphine-Induced Neuroinflammation.International journal of molecular sciences · 2024Article
- The association between the Glutathione S-transferase polymorphisms and addiction to opioids and methamphetamine in the Iranian population.Frontiers in psychiatry · 2024Article
- Substance Use and Addiction.Advances in neurobiology · 2024Review
- Multimodal Acute Pain Management in the Parturient with Opioid Use Disorder: A Review.Journal of pain research · 2024Review
- Genetically supported causality between gut microbiota, immune cells and morphine tolerance: a two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Each year, over 50 million Americans suffer from persistent pain, including debilitating headaches, joint pain, and severe back pain. Although morphine is amongst the most effective analgesics available for the management of severe pain, prolonged morphine treatment results in decreased analgesic efficacy (i.e., tolerance). Despite significant headway in the field, the mechanisms underlying the development of morphine tolerance are not well understood. The midbrain ventrolateral periaqueductal gray (vlPAG) is a primary neural substrate for the analgesic effects of morphine, as well as for the development of morphine tolerance. A growing body of literature indicates that activated glia (i.e., microglia and astrocytes) facilitate pain transmission and oppose morphine analgesia, making these cells important potential targets in the treatment of chronic pain. Morphine affects glia by binding to the innate immune receptor toll-like receptor 4 (TLR4), leading to the release of proinflammatory cytokines and opposition of morphine analgesia. Despite the established role of the vlPAG as an integral locus for the development of morphine tolerance, most studies have examined the role of glia activation within the spinal cord. Additionally, the role of TLR4 in the development of tolerance has not been elucidated. This review attempts to summarize what is known regarding the role of vlPAG glia and TLR4 in the development of morphine tolerance. These data, together, provide information about the mechanism by which central nervous system glia regulate morphine tolerance, and identify a potential therapeutic target for the enhancement of analgesic efficacy in the clinical treatment of chronic pain.
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What OpenQuestion holds
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.