ArticleNeurogastroenterology and motility2009
Protease-activated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity.
Article in Neurogastroenterology and motility, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 96 citations in OpenAlex.
- TRPV4-Mast Cell Interactions in Neurogenic Inflammation and Chronic Diseases: A Narrative Review.International journal of molecular sciences · 2026Review
- The Mast Cell-PAR2-TRP Axis: A Convergent Mechanism for Visceral Hypersensitivity Independent of Divergent Motility in IBS.Biomolecules · 2026Review
- Proteases and Abdominal Pain-Old Dog, New (Microbial) Tricks.Cellular and molecular gastroenterology and hepatology · 2026Review
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- The role of the gut microbiome in disorders of gut-brain interaction.The FEBS journal · 2025Review
- The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2025Review
- Electroacupuncture Relieves Visceral Hypersensitivity via Balancing PAR2 and PAR4 in the Descending Pain Modulatory System of Goats.Brain sciences · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- The Effect of Serine Protease Inhibitors on Visceral Pain in Different Rodent Models With an Intestinal Insult.Frontiers in pharmacology · 2022Article
- Physiology and Pathophysiology of Itch.Physiological reviews · 2020Review
- Proteinase Activated Receptor 4 in the Jejunum of Healthy Horses and of Horses With Epiploic Hernia.Frontiers in veterinary science · 2020Article
- Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.Frontiers in endocrinology · 2019Review
- Newly developed serine protease inhibitors decrease visceral hypersensitivity in a post-inflammatory rat model for irritable bowel syndrome.British journal of pharmacology · 2018Article
- Downregulation of iNOS, IL-1Journal of immunology research · 2018Article
- Existing and emerging therapies for managing constipation and diarrhea.Current opinion in pharmacology · 2017Review
- Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases.World journal of gastroenterology · 2016Review
- The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments.Journal of neurogastroenterology and motility · 2016Review
- Protease-activated receptor 4: from structure to function and back again.British journal of pharmacology · 2016Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protease-activated receptor-4 (PAR(4)) belongs to the family of receptors activated by the proteolytic cleavage of their extracellular N-terminal domain and the subsequent binding of the newly released N-terminus. While largely expressed in the colon, the role of PAR(4) in gut functions has not been defined. We have investigated the effects of PAR(4) agonist on colonic sensations and sensory neuron signalling, and its role in visceral pain. We observed that a single administration of the PAR(4) agonist peptide (AYPGKF-NH(2)), but not the control peptide (YAPGKF-NH(2)) into the colon lumen of mice significantly reduced the visceromotor response to colorectal distension at different pressures of distension. Further, intracolonic administration of the PAR(4) agonist, but not the control peptide, was able to significantly inhibit PAR(2) agonist- and transcient receptor potential vanilloid-4 (TRPV4) agonist-induced allodynia and hyperalgesia in response to colorectal distension. Protease-activated receptor-4 was detected in sensory neurons projecting from the colon, and isolated from the dorsal root ganglia, where it co-expressed with PAR(2) and TRPV4. In total sensory neurons, PAR(4) agonist exposure inhibited free intracellular calcium mobilization induced by the pro-nociceptive agonists of PAR(2) and TRPV4. Finally, PAR(4)-deficient mice experienced increased pain behaviour in response to intracolonic administration of mustard oil, compared with wild-type littermates. These results show that PAR(4) agonists modulate colonic nociceptive response, inhibit colonic hypersensitivity and primary afferent responses to pro-nociceptive mediators. Endogenous activation of PAR(4) also plays a major role in controlling visceral pain. These results identify PAR(4) as a previously unknown modulator of visceral nociception.
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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.