ArticleProceedings of the National Academy of Sciences of the United States of America2020
Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 105 citations in OpenAlex.
- Structure-guided allosteric modulation of the delta opioid receptor.Nature communications · 2026Article
- Applications of micro/nano drug delivery systems in cancer pain management.Bioactive materials · 2026Review
- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
- Breaking Through Cancer Pain: From Single-Drug Management to Multimodal Analgesia.Pain research & management · 2026Review
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.Frontiers in molecular neuroscience · 2026Article
- The neural circuits and signalling pathways of opioid use disorder.Nature reviews. Neuroscience · 2025Review
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.bioRxiv : the preprint server for biology · 2025Article
- Nanomedicines targeting protease-activated receptor 2 in endosomes provide sustained analgesia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025Review
- Delta opioid receptors: Overlooked outlier or the next big thing.Current opinion in pharmacology · 2025Review
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- Opioid receptors reveal a discrete cellular mechanism of endosomal G protein activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pain Signaling by GPCRs and RTKs.Trends in pharmacological sciences · 2025Review
- Trends and Hotspots in Nanomedicine Applications for Pain: A Bibliometric Analysis from 1999 to 2024.ACS omega · 2025Article
- A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.British journal of pharmacology · 2025Article
- Emerging advances in drug delivery systems (DDSs) for optimizing cancer complications.Materials today. Bio · 2025Review
- Subcellular activation of β-adrenergic receptors using a spatially restricted antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- Selective targeting of mu opioid receptors to primary cilia.Cell reports · 2024Article
- The Impact of UFP-512 in Mice with Osteoarthritis Pain: The Role of Hydrogen Sulfide.Antioxidants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 4 countries.
Funding
Abstract
Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients and mice with colitis released opioids that activated DOPr on nociceptors to cause a sustained decrease in excitability. DOPr agonists inhibited mechanically sensitive colonic nociceptors. DOPr endocytosis and endosomal signaling by protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways mediated the sustained inhibitory actions of endogenous opioids and DOPr agonists. DOPr agonists stimulated the recruitment of Gα
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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.