4.8 Article

Trypsin mediates nociception via the proteinase-activated receptor 2: A potentially novel role in pancreatic pain

Journal

GASTROENTEROLOGY
Volume 127, Issue 3, Pages 883-891

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2004.07.002

Keywords

-

Funding

  1. NIDDK NIH HHS [R01 DK62330-01] Funding Source: Medline

Ask authors/readers for more resources

Background & Aims: The pathogenesis of pain in pancreatitis remains poorly understood. We hypothesized that trypsin, a key inflammatory mediator in this condition, can also activate nociceptive neurons via the proteinase-activated receptor 2. Methods: Double immunohistochemical staining of T8 to T12 dorsal root ganglia sections was performed with antibodies against proteinase-activated receptor 2 and vanilloid receptor 1, a marker for primary nociceptive neurons. In vivo nociceptive activity was measured by FOS immunoreactivity in thoracic spinal dorsal horn segments after intrapancreatic administration of proteinase-activated receptor 2 agonists. Pain behavior was assessed by visceromotor reflex activity in response to noxious stimulation of the pancreas with proteinase-activated receptor 2 agonists. Results: Proteinase-activated receptor 2 was expressed by virtually all nociceptive neurons in thoracic dorsal root ganglia. Intraductal trypsin, in subinflammatory concentrations, activated spinal dorsal horn neurons in a dose-dependent manner, as measured by FOS expression. Both trypsin and a proteinase-activated receptor 2-specific peptide agonist induced a behavioral pain response when infused into the pancreatic duct of awake rats. Preinfusion of the pancreatic duct with proteinase-activated receptor 2-specific activating peptide desensitized the response to trypsin. Conclusions: Our findings suggest a novel proteinase-activated receptor 2-mediated role for trypsin in the pathogenesis of pancreatic pain and one that is independent of its inflammatory effect.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available