ArticlePsychopharmacology2017
Genetic dissociation of morphine analgesia from hyperalgesia in mice.
Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Synthesis and Pharmacology of a Morphinan-Derived Dual Mu-Kappa Opioid Receptor Agonist Analgesic.ACS chemical neuroscience · 2025Article
- Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.International journal of molecular sciences · 2025Review
- Brief Opioid Exposure Paradoxically Augments Primary Afferent Input to Spinal Excitatory Neurons via α2δ-1-Dependent Presynaptic NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology.Pharmacology & therapeutics · 2022Review
- Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene,Biomolecules · 2021Review
- Alternative Splicing of Opioid Receptor Genes Shows a Conserved Pattern for 6TM Receptor Variants.Cellular and molecular neurobiology · 2021Article
- Interactive Mechanisms of Supraspinal Sites of Opioid Analgesic Action: A Festschrift to Dr. Gavril W. Pasternak.Cellular and molecular neurobiology · 2021Review
- Synthesis of the Mechanisms of Opioid Tolerance: Do We Still Say NO?Cellular and molecular neurobiology · 2021Review
- Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane μ-opioid receptor isoforms.British journal of pharmacology · 2021Article
- TREK1 channel activation as a new analgesic strategy devoid of opioid adverse effects.British journal of pharmacology · 2020Article
- A Truncated Six Transmembrane Splice Variant MOR-1G Enhances Expression of the Full-Length Seven TransmembraneMolecular pharmacology · 2020Article
- Identification of Abundant and Evolutionarily Conserved Opioid Receptor Circular RNAs in the Nervous System Modulated by Morphine.Molecular pharmacology · 2019Article
- Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Molecular neurobiology · 2019Article
- Usefulness of knockout mice to clarify the role of the opioid system in chronic pain.British journal of pharmacology · 2018Review
- Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace.Neuropharmacology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleMorphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM).
objectivesThis study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions.
methodsGroups of male and mixed-gender wild-type and exon 11 Oprm1 knockout mice were examined in a series of behavioral assays measuring analgesia, hyperalgesia, respiration, and reward in conditioned place preference assays.
resultsLoss of the 6TM variants in an exon 11 knockout (E11 KO) mouse did not affect morphine analgesia, reward, or respiratory depression. However, E11 KO mice lacking 6TM variants failed to show morphine-induced hyperalgesia, developed tolerance more slowly than wild-type mice, and did not display hyperlocomotion.
conclusionsTogether, our findings confirm the established role of 7TM mu receptor variants in morphine analgesia, reward, and respiratory depression, but reveal an unexpected obligatory role for 6TM variants in morphine-induced hyperalgesia and a modulatory role in morphine tolerance and dependence.
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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.