ArticleCell2011
Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids.
Article in Cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
141 citing papers in PubMed, 1 synthesis or guideline pooled it, 290 citations in OpenAlex.
- Interventions for itch in people with advanced chronic kidney disease.The Cochrane database of systematic reviews · 2020Pooled it
- The Connections Between Pain and Itch: Shared Neuroimmune Mechanisms and Therapeutic Implications.Current pain and headache reports · 2026Review
- OPRM1/MRGPRX1 heterodimers drive opioid-induced itch through a peripheral mechanism.Journal of biomedical science · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Genetic Variation A118G in the OPRM1 Gene Underlies the Dimorphic Response to Epidural Opioid-Induced Itch.Neuroscience bulletin · 2025Article
- Central neural circuits underlying itch sensation.Nature reviews. Neuroscience · 2025Review
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Neuropeptide Y neurons mediate opioid-induced itch by disinhibiting GRP-GRPR microcircuits in the spinal cord.Nature communications · 2025Article
- Article
- Hair Loss in a Hemodialysis Patient after Repetitive Use of the Antipruritic Drug Nalfurafine: Implications of Impaired Angiogenesis for Hair Loss.Internal medicine (Tokyo, Japan) · 2025Article
- Histamine HBiomolecules · 2024Review
- STING controls opioid-induced itch and chronic itch via spinal tank-binding kinase 1-dependent type I interferon response in mice.Journal of neuroinflammation · 2023Article
- Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of GRPR in Acupuncture Intervention in the "Itch-scratch Vicious Cycle" Spinal Circuit of Chronic Pruritus.Chinese medicine · 2023Review
- Angelica Yinzi Alleviates Pruritus-Related Atopic Dermatitis through Skin Repair, Antioxidation, and Balancing PeripheralEvidence-based complementary and alternative medicine : eCAM · 2023Article
- Characterization of the expression of gastrin-releasing peptide and its receptor in the trigeminal and spinal somatosensory systems of Japanese macaque monkeys: Insight into humans.The Journal of comparative neurology · 2022Article
- Multiplexed Representation of Itch and Pain and Their Interaction in the Primary Somatosensory Cortex.Experimental neurobiology · 2022Article
- Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Mas-Related G Protein-Coupled Receptor-X2 and Its Role in Non-immunoglobulin E-Mediated Drug Hypersensitivity.Immunology and allergy clinics of North America · 2022Review
- Opioidergic Signaling-A Neglected, Yet Potentially Important Player in Atopic Dermatitis.International journal of molecular sciences · 2022Review
81 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal opioid-induced itch, a prevalent side effect of pain management, has been proposed to result from pain inhibition. We now report that the μ-opioid receptor (MOR) isoform MOR1D is essential for morphine-induced scratching (MIS), whereas the isoform MOR1 is required only for morphine-induced analgesia (MIA). MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, relaying itch information. We show that morphine triggers internalization of both GRPR and MOR1D, whereas GRP specifically triggers GRPR internalization and morphine-independent scratching. Providing potential insight into opioid-induced itch prevention, we demonstrate that molecular and pharmacologic inhibition of PLCβ3 and IP3R3, downstream effectors of GRPR, specifically block MIS but not MIA. In addition, blocking MOR1D-GRPR association attenuates MIS but not MIA. Together, these data suggest that opioid-induced itch is an active process concomitant with but independent of opioid analgesia, occurring via the unidirectional cross-activation of GRPR signaling by MOR1D heterodimerization.
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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.