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Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation.
- Source :
-
Gastroenterology [Gastroenterology] 2011 Apr; Vol. 140 (4), pp. 1283-1291.e1-2. Date of Electronic Publication: 2010 Dec 24. - Publication Year :
- 2011
-
Abstract
- Background & Aims: The transient receptor potential (TRP) channels TRPV1 and TRPA1 have each been associated with regulation of efferent properties of primary afferent neurons that initiate neurogenic inflammation and are required for the development of inflammatory hyperalgesia. To evaluate the role of these channels in producing pain during pancreatic inflammation, we studied pancreatic nodose ganglion (NG) and dorsal root ganglion (DRG) sensory neurons (identified by content of retrograde tracer) and behavioral outcomes in a mouse model of acute pancreatitis.<br />Methods: Pancreatic inflammation was induced by 8 hourly injections of cerulein (50 μg/kg). The extent of inflammation, pancreatic neuron TRP channel expression and function and excitability, and pain-related behaviors were evaluated over the course of the following week.<br />Results: Histology and myeloperoxidase activity confirmed pancreatic inflammation that was associated with increased excitability and messenger RNA expression of the TRP channels in NG and DRG pancreatic neurons. Calcium imaging of pancreatic NG and DRG neurons from mice given cerulein revealed increased responses to TRP agonists. TRPV1 and TRPA1 antagonists attenuated cerulein-induced pain behaviors and pancreatic inflammation; they had a synergistic effect.<br />Conclusions: Pancreatic inflammation significantly increased the expression and functional properties of TRPV1 and TRPA1, as well as the excitability of pancreatic sensory neurons in vagal and spinal pathways. TRP channel antagonists acted synergistically to reverse pancreatic inflammation and associated pain behaviors; reagents that target interactions between these channels might be developed to reduce pain in patients with acute pancreatitis.<br /> (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Acute Disease
Animals
Behavior, Animal drug effects
Calcium metabolism
Cells, Cultured
Disease Models, Animal
Ganglia, Spinal cytology
Ganglia, Spinal immunology
Ganglia, Spinal metabolism
Gene Expression immunology
Male
Mice
Mice, Inbred C57BL
Nodose Ganglion cytology
Nodose Ganglion immunology
Nodose Ganglion metabolism
Pancreas immunology
Pancreas innervation
Patch-Clamp Techniques
TRPA1 Cation Channel
TRPV Cation Channels antagonists & inhibitors
TRPV Cation Channels genetics
Transient Receptor Potential Channels antagonists & inhibitors
Transient Receptor Potential Channels genetics
Abdominal Pain drug therapy
Abdominal Pain etiology
Abdominal Pain immunology
Acetanilides pharmacology
Acrylamides pharmacology
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Pancreatitis complications
Pancreatitis drug therapy
Pancreatitis immunology
Purines pharmacology
TRPV Cation Channels immunology
Transient Receptor Potential Channels immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0012
- Volume :
- 140
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 21185837
- Full Text :
- https://doi.org/10.1053/j.gastro.2010.12.033