ReviewPharmacological reviews2013
Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.
Review in Pharmacological reviews, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03847311 (Double Blind Trial Investigating the Role of Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients), which is not on this map. Cited by 492 papers, 1 of them a synthesis that pooled it.
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.
Double Blind Trial Investigating the Role of Sulfasalazine in Decreasing Opioids Requirements in Breast Cancer Patients
Who cites it
492 citing papers in PubMed, 1 synthesis or guideline pooled it, 784 citations in OpenAlex.
- The organ-specific modulation of malignant processes by opioids: a systematic review of cell culture studies.British journal of cancer · 2025Pooled it
- An opioid-withholding human laboratory paradigm during opioid agonist treatment for opioid use disorder and chronic pain: Phase- and dose-dependent effects of cannabidiol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Spinorphin Attenuates Acute Experimental Seizures and Associated Neurochemical Alterations: Possible Involvement of Opioid Receptors.Neurochemical research · 2026Article
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- μ-Opioid receptors negatively regulate striatal dopamine DResearch square · 2026Article
- EphB1 Receptor Blockade Augments Morphine Antinociception via Inhibiting GRK2-Mediated µ-Opioid Receptor Internalization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Quantitative μ-Opioid Receptor PET with [Pharmaceutics · 2026Article
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Characterizing the Safety and Efficacy of Propofol in Critically Ill Pediatric Patients.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026Article
- The effect of clavulanic acid on the development of tolerance and dependence induced by morphine in mice: role of DRD2 and NR1 genes, oxidative stress, and GDNF protein.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Inflammatory Signal Persistence in Pain: Lymphatic Regulation and Neuroimmune Integration.Biology · 2026Review
- Molecular mechanism of allosteric modulation of opioid receptors.Signal transduction and targeted therapy · 2026Article
- Altered Intracellular Trafficking as a Mechanism for Prolonged Duration of G Protein-Coupled Receptor Activation.Journal of the American Chemical Society · 2026Article
- The actions of morphine on microglia and the underlying effects on associated adverse effects.Psychopharmacology · 2026Review
- Exploring the effects of cannabidiol on pain sensitivity using quantitative sensory testing among individuals receiving methadone or buprenorphine for opioid use disorder: an open-label, proof-of-concept study.Addictive behaviors reports · 2026Article
- Structure-Activity Relationships and Ligand-Dependent Arrestin Bias in μ-Opioid Receptor-Mediated ERK Activation.Biomolecules & therapeutics · 2026Article
- Mechanism-guided identification of antidepressant G protein-coupled receptor drug targets.Cell · 2026Article
- Glucocorticoid-endocannabinoid crosstalk in the ventrolateral periaqueductal gray (vlPAG) promotes pain resolution.bioRxiv : the preprint server for biology · 2026Article
- Persistent Mu-Opioid Receptor Dysregulation in a Pain-Facilitatory Brain Region Reinstates Hyperalgesia After Resolution of Opioid-Induced Hyperalgesia.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
432 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
Morphine and related µ-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain. A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists. Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists. Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress. This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms. Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial. The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail. While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids. Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance.
Indexed as
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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.