ArticleJCI insight2019
Activation of pruritogenic TGR5, MrgprA3, and MrgprC11 on colon-innervating afferents induces visceral hypersensitivity.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 84 citations in OpenAlex.
- Elobixibat improves rectal sensation in patients with chronic constipation aged ≥60 years: a randomised placebo-controlled study.BMJ open gastroenterology · 2023Trial
- Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.Journal of neuroinflammation · 2026Article
- GABAExperimental physiology · 2026Article
- MrgprC11 expression and function in vagal afferent nerves in the esophagus.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Mas-Related G-Protein-Coupled Receptors: Emerging Roles in Neuropathic Pain.Biomolecules · 2026Review
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.Frontiers in molecular neuroscience · 2026Article
- Endosomal MrGPRX1 signaling sensitizes TRPV1 to enhance itch.bioRxiv : the preprint server for biology · 2025Article
- Neurogenic inflammation and itch in barrier tissues.Seminars in immunology · 2025Review
- Bile acid signaling mediates gut microbiota regulation of host lipid metabolism.Frontiers in microbiology · 2025Review
- Mast cell modulation: A novel therapeutic strategy for abdominal pain in irritable bowel syndrome.Cell reports. Medicine · 2024Review
- Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.Cells · 2024Review
- The potential mechanism of action of gut flora and bile acids through the TGR5/TRPV1 signaling pathway in diabetic peripheral neuropathic pain.Frontiers in endocrinology · 2024Review
- Altered gut microbiota-host bile acid metabolism in IBS-D patients with liver depression and spleen deficiency pattern.Chinese medicine · 2023Article
- Article
- Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.Frontiers in molecular neuroscience · 2023Article
- Bile Acid and Gut Microbiota in Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2022Review
- Tauroursodeoxycholic Acid Reduces Neuroinflammation but Does Not Support Long Term Functional Recovery of Rats with Spinal Cord Injury.Biomedicines · 2022Article
- TGR5 agonists induce peripheral and central hypersensitivity to bladder distension.Scientific reports · 2022Article
- Sustained endosomal release of a neurokinin-1 receptor antagonist from nanostars provides long-lasting relief of chronic pain.Biomaterials · 2022Article
- Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.Trends in pharmacological sciences · 2022Review
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
Itch induces scratching that removes irritants from the skin, whereas pain initiates withdrawal or avoidance of tissue damage. While pain arises from both the skin and viscera, we investigated whether pruritogenic irritant mechanisms also function within visceral pathways. We show that subsets of colon-innervating sensory neurons in mice express, either individually or in combination, the pruritogenic receptors Tgr5 and the Mas-gene-related GPCRs Mrgpra3 and Mrgprc11. Agonists of these receptors activated subsets of colonic sensory neurons and evoked colonic afferent mechanical hypersensitivity via a TRPA1-dependent mechanism. In vivo intracolonic administration of individual TGR5, MrgprA3, or MrgprC11 agonists induced pronounced visceral hypersensitivity to colorectal distension. Coadministration of these agonists as an "itch cocktail" augmented hypersensitivity to colorectal distension and changed mouse behavior. These irritant mechanisms were maintained and enhanced in a model of chronic visceral hypersensitivity relevant to irritable bowel syndrome. Neurons from human dorsal root ganglia also expressed TGR5, as well as the human ortholog MrgprX1, and showed increased responsiveness to pruritogenic agonists in pathological states. These data support the existence of an irritant-sensing system in the colon that is a visceral representation of the itch pathways found in skin, thereby contributing to sensory disturbances accompanying common intestinal disorders.
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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.