ArticleThe Journal of physiology2007
Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 61 citations in OpenAlex.
- Monoclonal antibody inhibition of PAR2 reduces phenotype severity and pain in murine inflammatory bowel disease.Pain reports · 2026Article
- Article
- Electrophysiological and Proteomic Evidence of Protease-Mediated Pro-nociceptive Signaling in Inflammatory Bowel Disease Patients.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- A Bacteroides fragilis protease activates host PARCell host & microbe · 2025Article
- Emerging therapeutic approaches for treating abdominal pain.Journal of the Canadian Association of Gastroenterology · 2025Review
- The gut-brain axis and pain signalling mechanisms in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2025Review
- Electroacupuncture Regulates TRPV1 through PAR2/PKC Pathway to Alleviate Visceral Hypersensitivity in FD Rats.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Enhancement by TNF-α of TTX-resistant NaAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Nociceptor Signalling through ion Channel Regulation via GPCRs.International journal of molecular sciences · 2019Review
- Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Delayed Effect of the Light Pulse on Phosphorylated ERK1/2 and GSK3β Kinases in the Ventrolateral Suprachiasmatic Nucleus of Rat.Journal of molecular neuroscience : MN · 2015Article
- Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain.The Journal of biological chemistry · 2015Article
- Article
- Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain.PloS one · 2015Article
- The TGR5 receptor mediates bile acid-induced itch and analgesia.The Journal of clinical investigation · 2013Article
- Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation.American journal of physiology. Gastrointestinal and liver physiology · 2012Article
- Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.Neurogastroenterology and motility · 2012Article
- Essential role of mast cells in the visceral hyperalgesia induced by T. spiralis infection and stress in rats.Mediators of inflammation · 2012Article
- The multiple pathways for itch and their interactions with pain.Trends in neurosciences · 2010Review
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 2 institutions in 2 countries.
Funding
Abstract
Agonists of protease-activated receptor 2 (PAR(2)) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR(2)-evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI-labelled neurons contained PAR(2) immunoreactivity, confirming the presence of receptors on colonic neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR(2) activation with a brief application (3 min) of PAR(2) agonists, SLIGRL-NH(2) and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL-NH(2) markedly suppressed delayed rectifier I(K) currents (55% at 10 min), but had no effect on the transient I(A) current or TTX-resistant Na(+) currents. In whole-cell current-clamp recordings, the sustained excitability evoked by PAR(2) activation was blocked by the PKC inhibitor, calphostin, and the ERK(1/2) inhibitor PD98059. Studies of ERK(1/2) phosphorylation using confocal microscopy demonstrated that SLIGRL-NH(2) increased levels of immunoreactive pERK(1/2) in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR(2) receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier I(K) currents. Both PKC and ERK(1/2) mediate the PAR(2)-induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.
Indexed as
Identifiers
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.