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

Willemijntje A. Hoogerwerf, Mohan Shenoy, John Winston, Shu Yuan Xiao, Zhijun He, Pankaj J. Pasricha

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)883-891
Number of pages9
JournalGastroenterology
Volume127
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

PAR-2 Receptor
Nociception
Trypsin
Pain
Nociceptors
Pancreatic Ducts
Spinal Ganglia
Thorax
Posterior Horn Cells
Peptides
Pancreatitis
Reflex
Pancreas
Staining and Labeling
Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Trypsin mediates nociception via the proteinase-activated receptor 2 : A potentially novel role in pancreatic pain. / Hoogerwerf, Willemijntje A.; Shenoy, Mohan; Winston, John; Xiao, Shu Yuan; He, Zhijun; Pasricha, Pankaj J.

In: Gastroenterology, Vol. 127, No. 3, 09.2004, p. 883-891.

Research output: Contribution to journalArticle

Hoogerwerf, Willemijntje A. ; Shenoy, Mohan ; Winston, John ; Xiao, Shu Yuan ; He, Zhijun ; Pasricha, Pankaj J. / Trypsin mediates nociception via the proteinase-activated receptor 2 : A potentially novel role in pancreatic pain. In: Gastroenterology. 2004 ; Vol. 127, No. 3. pp. 883-891.
@article{3f17b4b890ef4039af7b810de2e176db,
title = "Trypsin mediates nociception via the proteinase-activated receptor 2: A potentially novel role in pancreatic pain",
abstract = "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.",
author = "Hoogerwerf, {Willemijntje A.} and Mohan Shenoy and John Winston and Xiao, {Shu Yuan} and Zhijun He and Pasricha, {Pankaj J.}",
year = "2004",
month = "9",
doi = "10.1053/j.gastro.2004.07.002",
language = "English (US)",
volume = "127",
pages = "883--891",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Trypsin mediates nociception via the proteinase-activated receptor 2

T2 - A potentially novel role in pancreatic pain

AU - Hoogerwerf, Willemijntje A.

AU - Shenoy, Mohan

AU - Winston, John

AU - Xiao, Shu Yuan

AU - He, Zhijun

AU - Pasricha, Pankaj J.

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4444301767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444301767&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2004.07.002

DO - 10.1053/j.gastro.2004.07.002

M3 - Article

C2 - 15362043

AN - SCOPUS:4444301767

VL - 127

SP - 883

EP - 891

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -