Tags

Type your tag names separated by a space and hit enter

Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation.
Gastroenterology. 2011 Apr; 140(4):1283-1291.e1-2.G

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.

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.

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.

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.

Authors+Show Affiliations

Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. schwartzee@upmc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21185837

Citation

Schwartz, Erica S., et al. "Synergistic Role of TRPV1 and TRPA1 in Pancreatic Pain and Inflammation." Gastroenterology, vol. 140, no. 4, 2011, pp. 1283-1291.e1-2.
Schwartz ES, Christianson JA, Chen X, et al. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology. 2011;140(4):1283-1291.e1-2.
Schwartz, E. S., Christianson, J. A., Chen, X., La, J. H., Davis, B. M., Albers, K. M., & Gebhart, G. F. (2011). Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology, 140(4), 1283-e1-2. https://doi.org/10.1053/j.gastro.2010.12.033
Schwartz ES, et al. Synergistic Role of TRPV1 and TRPA1 in Pancreatic Pain and Inflammation. Gastroenterology. 2011;140(4):1283-1291.e1-2. PubMed PMID: 21185837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. AU - Schwartz,Erica S, AU - Christianson,Julie A, AU - Chen,Xiaowei, AU - La,Jun-Ho, AU - Davis,Brian M, AU - Albers,Kathryn M, AU - Gebhart,G F, Y1 - 2010/12/24/ PY - 2010/04/06/received PY - 2010/12/10/revised PY - 2010/12/20/accepted PY - 2010/12/28/entrez PY - 2010/12/28/pubmed PY - 2011/5/27/medline SP - 1283-1291.e1-2 JF - Gastroenterology JO - Gastroenterology VL - 140 IS - 4 N2 - 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. 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. 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. 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/21185837/Synergistic_role_of_TRPV1_and_TRPA1_in_pancreatic_pain_and_inflammation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(10)01878-0 DB - PRIME DP - Unbound Medicine ER -