ArticleFrontiers in molecular neuroscience2019
Internalized GPCRs as Potential Therapeutic Targets for the Management of Pain.
Article in Frontiers in molecular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 38 citations in OpenAlex.
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- Folding, misfolding, and regulation of intracellular traffic of G protein-coupled receptors involved in the hypothalamic-pituitary-gonadal axis.Andrology · 2026Review
- Novel GαGTP Sensors Reveal Endogenous and Subcellular G Protein Signaling Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Radiofrequency Ablation for Chronic Pain: Mechanistic Insights and Emerging Innovations.Cureus · 2025Review
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- Investigating the effects of global gene knockout of MrgF on motor performance and pain sensitivity in mice.Hereditas · 2025Article
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Orphan G protein-coupled receptors: the ongoing search for a home.Frontiers in pharmacology · 2024Review
- Prescription Trends in Complex Regional Pain Syndrome: A Retrospective Case-Control Study.Brain sciences · 2023Article
- Targeting endosomal receptors, a new direction for polymers in nanomedicine.Journal of materials chemistry. B · 2023Review
- A multi-dimensional view of context-dependent G protein-coupled receptor function.Biochemical Society transactions · 2023Review
- Novel Fluorescently Labeled PACAP and VIP Highlight Differences between Peptide Internalization and Receptor Pharmacology.ACS pharmacology & translational science · 2023Article
- Identification of key factors driving inflammation-induced sensitization of muscle sensory neurons.Frontiers in neuroscience · 2023Article
- Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.Nature communications · 2022Article
- Fragile X premutation carrier screening in Pakistani preconception women in primary care consultation.BMC women's health · 2022Article
- Specific motifs mediate post-synaptic and surface transport of G protein-coupled receptors.iScience · 2022Article
- Dynamics of intracellular neonatal Fc receptor-ligand interactions in primary macrophages using biophysical fluorescence techniques.Molecular biology of the cell · 2022Article
- Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics.Clinical & translational immunology · 2022Review
- Cellular and Molecular Machinery of Neuropathic Pain: an Emerging Insight.Current pharmacology reports · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peripheral and central neurons in the pain pathway are well equipped to detect and respond to extracellular stimuli such as pro-inflammatory mediators and neurotransmitters through the cell surface expression of receptors that can mediate rapid intracellular signaling. Following injury or infection, activation of cell surface G protein-coupled receptors (GPCRs) initiates cell signaling processes that lead to the generation of action potentials in neurons or inflammatory responses such as cytokine secretion by immune cells. However, it is now appreciated that cell surface events alone may not be sufficient for all receptors to generate their complete signaling repertoire. Following an initial wave of signaling at the cell surface, active GPCRs can engage with endocytic proteins such as the adaptor protein β-arrestin (βArr) to promote clathrin-mediated internalization. Classically, βArr-mediated internalization of GPCRs was hypothesized to terminate signaling, yet for multiple GPCRs known to contribute to pain, it has been demonstrated that endocytosis can also promote a unique "second wave" of signaling from intracellular membranes, including those of endosomes and the Golgi, that is spatiotemporally distinct from initial cell-surface events. In the context of pain, understanding the cellular and molecular mechanisms that drive spatiotemporal signaling of GPCRs is invaluable for understanding how pain occurs and persists, and how current analgesics achieve efficacy or promote side-effects. This review article discusses the importance of receptor localization for signaling outcomes of pro- and anti-nociceptive GPCRs, and new analgesic opportunities emerging through the development of "location-biased" ligands that favor binding with intracellular GPCR populations.
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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.