ArticleThe Journal of clinical investigation2023
Intestinal neuropod cell GUCY2C regulates visceral pain.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The gut neuroepithelial unit as a neurodegeneration-relevant interface in the gut-brain axis.Translational neurodegeneration · 2026Review
- Gut distension evokes rapid neural dynamics in vagal and hindbrain populations of larval zebrafish.iScience · 2026Article
- From Epithelial Sensing to Visceral Pain: Neuropod and Enterochromaffin Cells in Gut Neuroepithelial Circuits.International journal of molecular sciences · 2026Review
- Mechanisms and clinical implications of gut-brain interactions.The Journal of clinical investigation · 2026Review
- Reviewing the Peripheral and Central Mechanisms of Visceral Hypersensitivity in Intestinal Disorders.International journal of medical sciences · 2026Review
- Gut reactions and gut instincts: regulation of intestinal homeostasis by receptor guanylyl cyclase C (GC-C).The Biochemical journal · 2025Review
- Integration of signal transduction pathways in sensory epithelial enteroendocrine cells.Molecular biology of the cell · 2025Review
- Microbiota-neuroepithelial signalling across the gut-brain axis.Nature reviews. Microbiology · 2025Review
- Gene Expression Signatures of Porcine Bone Marrow-Derived Antigen-Presenting Cells Infected with Classical Swine Fever Virus.Viruses · 2025Article
- Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells.Nature methods · 2024Article
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- The Coding Logic of Interoception.Annual review of physiology · 2024Review
- Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain.Journal of neurochemistry · 2023Review
- Reduced Plasma Guanylin Levels Following EnterotoxigenicMicroorganisms · 2023Article
- Intestinal Enteroendocrine Cells: Present and Future Druggable Targets.International journal of molecular sciences · 2023Review
- Guanylyl cyclase C ameliorates visceral pain: an unsuspected link.The Journal of clinical investigation · 2023Article
- Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting number of evoked action potentials. Conversely, the GUCY2C agonist linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient - but not GUCY2C-deficient - neuropod cells, an effect independent of bulk epithelial cells or extracellular cGMP. Genetic elimination of intestinal GUCY2C amplified nociceptive signaling in VP that was comparable with chemically induced VP but refractory to linaclotide. Importantly, eliminating GUCY2C selectively in neuropod cells also increased nociceptive signaling and VP that was refractory to linaclotide. In the context of loss of GUCY2C hormones in patients with VP, these observations suggest a specific role for neuropod GUCY2C signaling in the pathophysiology and treatment of these pain syndromes.
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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.