ReviewGut2021
Targeting G protein-coupled receptors for the treatment of chronic pain in the digestive system.
Review in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 31 citations in OpenAlex.
- G Protein-Coupled Receptors in Irritable Bowel Syndrome: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Diagnosis, Prognosis, and Drug Target Discovery for Chronic Widespread Pain: A Large Proteogenomic Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Protease-Activated Receptor 2 Activation Provokes an Increase in Intracellular Calcium and Serotonin Secretion in a Human Enteroendocrine Cell Line.Cell biochemistry and function · 2025Article
- Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025Review
- Large-Scale Plasma Proteomics to Profile Pathways and Prognosis of Chronic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Gut microbial characteristics of the damp-heat constitution: a population-based multicenter cross-sectional study.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- A deep learning framework combining molecular image and protein structural representations identifies candidate drugs for pain.Cell reports methods · 2024Article
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Review
- An Update of G-Protein-Coupled Receptor Signaling and Its Deregulation in Gastric Carcinogenesis.Cancers · 2023Review
- Article
- GPCR Intracellular Loop Regulation of Beta-Arrestin-Mediated Endosomal Signaling Dynamics.Journal of molecular neuroscience : MN · 2022Article
- Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS.Frontiers in physiology · 2022Review
- Predictive Factors for Acute Postoperative Pain After Open Radical Gastrectomy for Gastric Cancer.Frontiers in public health · 2022Article
- RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation.Frontiers in cell and developmental biology · 2022Article
- Developing nociceptor-selective treatments for acute and chronic pain.Science translational medicine · 2021Article
- New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders.Gastroenterology · 2021Review
- GPR171 Agonist Reduces Chronic Neuropathic and Inflammatory Pain in Male, But Not Female Mice.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- G Protein-Coupled Receptors in Osteoarthritis: A Novel Perspective on Pathogenesis and Treatment.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Chronic pain is a hallmark of functional disorders, inflammatory diseases and cancer of the digestive system. The mechanisms that initiate and sustain chronic pain are incompletely understood, and available therapies are inadequate. This review highlights recent advances in the structure and function of pronociceptive and antinociceptive G protein-coupled receptors (GPCRs) that provide insights into the mechanisms and treatment of chronic pain. This knowledge, derived from studies of somatic pain, can guide research into visceral pain. Mediators from injured tissues transiently activate GPCRs at the plasma membrane of neurons, leading to sensitisation of ion channels and acute hyperexcitability and nociception. Sustained agonist release evokes GPCR redistribution to endosomes, where persistent signalling regulates activity of channels and genes that control chronic hyperexcitability and nociception. Endosomally targeted GPCR antagonists provide superior pain relief in preclinical models. Biased agonists stabilise GPCR conformations that favour signalling of beneficial actions at the expense of detrimental side effects. Biased agonists of µ-opioid receptors (MOPrs) can provide analgesia without addiction, respiratory depression and constipation. Opioids that preferentially bind to MOPrs in the acidic microenvironment of diseased tissues produce analgesia without side effects. Allosteric modulators of GPCRs fine-tune actions of endogenous ligands, offering the prospect of refined pain control. GPCR dimers might function as distinct therapeutic targets for nociception. The discovery that GPCRs that control itch also mediate irritant sensation in the colon has revealed new targets. A deeper understanding of GPCR structure and function in different microenvironments offers the potential of developing superior treatments for GI pain.
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What OpenQuestion holds
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.