ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
Serine proteases mediate inflammatory pain in acute pancreatitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.Journal of gastroenterology · 2020Trial
- From Inflammation to Neuroplasticity: Molecular Mechanisms of Pain in Acute, Recurrent and Chronic Pancreatitis.International journal of molecular sciences · 2026Review
- Optimising Pain Relief in Acute Pancreatitis: An Evidence-Based Approach.Journal of clinical medicine · 2025Review
- Pain intensity and prognosis of acute pancreatitis in an international, prospective study.The British journal of surgery · 2025Article
- Arachidonate 15-lipoxygenase: A promising therapeutic target for alleviating inflammation in acute pancreatitis.World journal of gastroenterology · 2025Review
- Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation.Chinese journal of integrative medicine · 2024Article
- Article
- Molecular mechanisms of pain in acute pancreatitis: recent basic research advances and therapeutic implications.Frontiers in molecular neuroscience · 2023Review
- Article
- A Mouse Model for Chronic Pancreatitis via Bile Duct TNBS Infusion.Journal of visualized experiments : JoVE · 2021Article
- Novel Analgesics with Peripheral Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.Pancreas · 2019Review
- Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain.Oncotarget · 2017Article
- Fluorescent diphenylphosphonate-based probes for detection of serine protease activity during inflammation.Bioorganic & medicinal chemistry letters · 2017Article
- Mesotrypsin Has Evolved Four Unique Residues to Cleave Trypsin Inhibitors as Substrates.The Journal of biological chemistry · 2015Article
- Effect of endogenous cholecystokinin on the course of acute pancreatitis in rats.World journal of gastroenterology · 2015Article
- Serine proteases and protease-activated receptor 2 mediate the proinflammatory and algesic actions of diverse stimulants.British journal of pharmacology · 2014Article
- Proteolytic activation of the human epithelial sodium channel by trypsin IV and trypsin I involves distinct cleavage sites.The Journal of biological chemistry · 2014Article
- Protease-activated receptors as therapeutic targets in visceral pain.Current neuropharmacology · 2013Article
- Corticotropin-releasing factor receptor 2 mediates sex-specific cellular stress responses.Molecular medicine (Cambridge, Mass.) · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute pancreatitis is a life-threatening inflammatory disease characterized by abdominal pain of unknown etiology. Trypsin, a key mediator of pancreatitis, causes inflammation and pain by activating protease-activated receptor 2 (PAR(2)), but the isoforms of trypsin that cause pancreatitis and pancreatic pain are unknown. We hypothesized that human trypsin IV and rat P23, which activate PAR(2) and are resistant to pancreatic trypsin inhibitors, contribute to pancreatic inflammation and pain. Injections of a subinflammatory dose of exogenous trypsin increased c-Fos immunoreactivity, indicative of spinal nociceptive activation, but did not cause inflammation, as assessed by measuring serum amylase and myeloperoxidase activity and by histology. The same dose of trypsin IV and P23 increased some inflammatory end points and caused a more robust effect on nociception, which was blocked by melagatran, a trypsin inhibitor that also inhibits polypeptide-resistant trypsin isoforms. To determine the contribution of endogenous activation of trypsin and its minor isoforms, recombinant enterokinase (ENK), which activates trypsins in the duodenum, was administered into the pancreas. Intraductal ENK caused nociception and inflammation that were diminished by polypeptide inhibitors, including soybean trypsin inhibitor and a specific trypsin inhibitor (type I-P), and by melagatran. Finally, the secretagogue cerulein induced pancreatic nociceptive activation and nocifensive behavior that were reversed by melagatran. Thus trypsin and its minor isoforms mediate pancreatic pain and inflammation. In particular, the inhibitor-resistant isoforms trypsin IV and P23 may be important in mediating prolonged pancreatic inflammatory pain in pancreatitis. Our results suggest that inhibitors of these isoforms could be novel therapies for pancreatitis pain.
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.