ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 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
138 citing papers in PubMed, 266 citations in OpenAlex.
- Dynamic Pathway Selectivity of TAS2R5 toward or Away from β-Arrestin or G Protein from Biased Agonists.Biochemistry · 2026Article
- Knowledge graph and emerging trends in β-arrestin research on pain: a bibliometric analysis (1997-2025).Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Distinct contributions of mu opioid and CB2 cannabinoid receptors to neuroimmune and behavioral responses.Advances in drug and alcohol research · 2026Article
- Narrative review of the scientific and methodological explanations for 101 mechanisms of opioid tolerance.Pain reports · 2025Article
- Role of β-Arrestin 2 in the antinociceptive and side effect profile of morphine and the novel mu opioid receptor agonists, kurkinorin and kurkinol.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Structural and dynamic insights into the biased signaling mechanism of the human kappa opioid receptor.Nature communications · 2025Article
- Sanguinarine-Chelerythrine fromPharmaceutics · 2025Article
- Biased Opioid Receptor Agonists: Balancing Analgesic Efficacy and Side-Effect Profiles.International journal of molecular sciences · 2025Review
- Impact of Intracellular Proteins on μ-Opioid Receptor Structure and Ligand Binding.The journal of physical chemistry. B · 2025Article
- Kratom: A Narrative Review of the Possible Clinical Uses and Dangers of This Opioid-Like Plant.Cureus · 2024Review
- Opioid system and related ligands: from the past to future perspectives.Journal of anesthesia, analgesia and critical care · 2024Review
- Mechanisms of cannabinoid tolerance.Biochemical pharmacology · 2023Review
- The Downregulation of Opioid Receptors and Neuropathic Pain.International journal of molecular sciences · 2023Review
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Design and development of novel, short, stable dynorphin-based opioid agonists for safer analgesic therapy.Frontiers in pharmacology · 2023Article
- Functional selectivity of EM-2 analogs at the mu-opioid receptor.Frontiers in pharmacology · 2023Article
- Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids.Acta pharmaceutica Sinica. B · 2023Article
- Upregulation of Brain's Calcium Binding Proteins in Mitragynine Dependence: A Potential Cellular Mechanism to Addiction.International journal of medical sciences · 2023Article
- Exploring pharmacological inhibition of GBritish journal of pharmacology · 2022Article
- Article
78 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Morphine induces antinociception by activating mu opioid receptors (muORs) in spinal and supraspinal regions of the CNS. (Beta)arrestin-2 (beta)arr2), a G-protein-coupled receptor-regulating protein, regulates the muOR in vivo. We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. To determine the general applicability of the (beta)arr2-muOR interaction in other neuronal systems, we have, in the present study, tested (beta)arr2 knock-out ((beta)arr2-KO) mice using the warm water tail-immersion paradigm, which primarily assesses spinal reflexes to painful thermal stimuli. In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Interestingly, however, after a delayed onset, they do ultimately develop morphine tolerance, although to a lesser degree than the wild-type (WT) controls. In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. These findings provide in vivo evidence that the muOR is differentially regulated in diverse regions of the CNS. Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent.
Indexed as
Identifiers
12451149PMC6758751W2110045591What 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.