ReviewFrontiers in molecular neuroscience2020
Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling as a Potential Target for Pain Management.
Review in Frontiers in molecular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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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
28 citing papers in PubMed, 46 citations in OpenAlex.
- G protein regulatory network shapes magnitude and kinetics of behavioral responses in an engineered opioid receptor model.The Journal of biological chemistry · 2026Article
- BMSCs regulate RGS3 expression in ovarian stromal cells to improve ovarian stromal fibrosis and angiogenic microenvironment in cyclophosphamide-induced premature ovarian failure.Stem cell research & therapy · 2026Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- The role of RGS12 in tissue repair and human diseases.Genes & diseases · 2025Review
- Dynamic regulation ofFrontiers in cell and developmental biology · 2025Article
- Social Isolation Induces Changes in the Monoaminergic Signalling in the Rat Medial Prefrontal Cortex.Cells · 2024Article
- Analgesic Peptides: From Natural Diversity to Rational Design.Molecules (Basel, Switzerland) · 2024Review
- Review
- Article
- Tianeptine promotes lasting antiallodynic effects in a mouse model of neuropathic pain.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Review
- The roles of ubiquitin-proteasome system and regulator of G protein signaling 4 in behavioral sensitization induced by a single morphine exposure.Brain and behavior · 2023Article
- Prognostic value of RGS1 and mTOR Immunohistochemical expression in Egyptian multiple myeloma patients; A single center study.PloS one · 2023Article
- A Regional and Projection-Specific Role of RGSz1 in the Ventrolateral Periaqueductal Grey in the Modulation of Morphine Reward.Molecular pharmacology · 2023Article
- Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review.Journal of personalized medicine · 2022Review
- Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake.Translational psychiatry · 2022Article
- Differential expression ofDrug and alcohol dependence reports · 2022Article
- A Novel Morphine Drinking Model of Opioid Dependence in Rats.International journal of molecular sciences · 2022Article
- Chronic paternal morphine exposure increases sensitivity to morphine-derived pain relief in male progeny.Science advances · 2022Article
- Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders.Frontiers in neural circuits · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Opioid drugs are the gold standard for the management of pain, but their use is severely limited by dangerous and unpleasant side effects. All clinically available opioid analgesics bind to and activate the mu-opioid receptor (MOR), a heterotrimeric G-protein-coupled receptor, to produce analgesia. The activity of these receptors is modulated by a family of intracellular RGS proteins or regulators of G-protein signaling proteins, characterized by the presence of a conserved RGS Homology (RH) domain. These proteins act as negative regulators of G-protein signaling by serving as GTPase accelerating proteins or GAPS to switch off signaling by both the Gα and βγ subunits of heterotrimeric G-proteins. Consequently, knockdown or knockout of RGS protein activity enhances signaling downstream of MOR. In this review we discuss current knowledge of how this activity, across the different families of RGS proteins, modulates MOR activity, as well as activity of other members of the opioid receptor family, and so pain and analgesia in animal models, with particular emphasis on RGS4 and RGS9 families. We discuss inhibition of RGS proteins with small molecule inhibitors that bind to sensitive cysteine moieties in the RH domain and the potential for targeting this family of intracellular proteins as adjuncts to provide an opioid sparing effect or as standalone analgesics by promoting the activity of endogenous opioid peptides. Overall, we conclude that RGS proteins may be a novel drug target to provide analgesia with reduced opioid-like side effects, but that much basic work is needed to define the roles for specific RGS proteins, particularly in chronic pain, as well as a need to develop newer inhibitors.
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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.