ArticleMolecular pain2011
Analgesic tone conferred by constitutively active mu opioid receptors in mice lacking β-arrestin 2.
Article in Molecular pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- The role of mu-opioid receptors in pancreatic islet α-cells.Journal of molecular endocrinology · 2025Article
- The role of mu-opioid receptors in pancreatic islet alpha cells.bioRxiv : the preprint server for biology · 2024Article
- Ligand-Free Signaling of G-Protein-Coupled Receptors: Relevance to μ Opioid Receptors in Analgesia and Addiction.Molecules (Basel, Switzerland) · 2022Review
- Postsurgical Latent Pain Sensitization Is Driven by Descending Serotonergic Facilitation and Masked by µ-Opioid Receptor Constitutive Activity in the Rostral Ventromedial Medulla.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Transport of Maternally Administered Pharmaceutical Agents Across the Placental Barrier In Vitro.ACS applied bio materials · 2022Article
- Src Kinase Inhibition Attenuates Morphine Tolerance without Affecting Reinforcement or Psychomotor Stimulation.Anesthesiology · 2017Article
- Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src.Scientific reports · 2017Article
- Constitutive Desensitization of Opioid Receptors in Peripheral Sensory Neurons.The Journal of pharmacology and experimental therapeutics · 2016Article
- Sustained Suppression of Hyperalgesia during Latent Sensitization by μ-, δ-, and κ-opioid receptors and α2A Adrenergic Receptors: Role of Constitutive Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Maturational alterations in constitutive activity of medial prefrontal cortex kappa-opioid receptors in Wistar rats.Journal of neurochemistry · 2015Article
- Latent sensitization: a model for stress-sensitive chronic pain.Current protocols in neuroscience · 2015Article
- The opioid receptor pharmacology of GSK1521498 compared to other ligands with differential effects on compulsive reward-related behaviours.Psychopharmacology · 2015Article
- The vital role of constitutive GPCR activity in the mesolimbic dopamine system.Translational psychiatry · 2014Review
- β-arrestins: regulatory role and therapeutic potential in opioid and cannabinoid receptor-mediated analgesia.Handbook of experimental pharmacology · 2014Review
- Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.Science (New York, N.Y.) · 2013Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
- Morphine withdrawal enhances constitutive μ-opioid receptor activity in the ventral tegmental area.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Evidence that behavioral phenotypes of morphine in β-arr2-/- mice are due to the unmasking of JNK signaling.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012Article
- Endogenous analgesia, dependence, and latent pain sensitization.Current topics in behavioral neurosciencesArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Hedonic reward, dependence and addiction are unwanted effects of opioid analgesics, linked to the phasic cycle of μ opioid receptor activation, tolerance and withdrawal. In vitro studies of recombinant G protein coupled receptors (GPCRs) over expressed in cell lines reveal an alternative tonic signaling mechanism that is independent of agonist. Such studies demonstrate that constitutive GPCR signaling can be inhibited by inverse agonists but not by neutral antagonists. However, ligand-independent activity has been difficult to examine in vivo, at the systems level, due to relatively low levels of constitutive activity of most GPCRs including μ receptors, often necessitating mutagenesis or pharmacological manipulation to enhance basal signaling. We previously demonstrated that the absence of β-arrestin 2 (β-arr2) augments the constitutive coupling of μ receptors to voltage-activated Ca²+ channels in primary afferent dorsal root ganglion neurons from β-arr2⁻/⁻ mice. We used this in vitro approach to characterize neutral competitive antagonists and inverse agonists of the constitutively active wild type μ receptors in neurons. We administered these agents to β-arr2⁻/⁻ mice to explore the role of constitutive μ receptor activity in nociception and hedonic tone. This study demonstrates that the induction of constitutive μ receptor activity in vivo in β-arr2⁻/⁻ mice prolongs tail withdrawal from noxious heat, a phenomenon that was reversed by inverse agonists, but not by antagonists that lack negative efficacy. By contrast, the aversive effects of inverse agonists were similar in β-arr2⁻/⁻ and β-arr2+/+ mice, suggesting that hedonic tone was unaffected.
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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.