Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation

Erica S. Schwartz, Julie A. Christianson, Xiaowei Chen, Jun-Ho La, Brian M. Davis, Kathryn M. Albers, G. F. Gebhart

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1283-1291
Number of pages9
JournalGastroenterology
Volume140
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

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Transient Receptor Potential Channels
Inflammation
Pain
Nodose Ganglion
Ceruletide
Spinal Ganglia
Sensory Receptor Cells
Neurons
Pancreatitis
Neurogenic Inflammation
Afferent Neurons
Hyperalgesia
Peroxidase
Histology
Calcium
Messenger RNA
Injections

Keywords

  • Analgesia
  • Nervous System
  • Pain Relief
  • Pancreas

ASJC Scopus subject areas

  • Gastroenterology

Cite this

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), 1283-1291. https://doi.org/10.1053/j.gastro.2010.12.033

Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. / Schwartz, Erica S.; Christianson, Julie A.; Chen, Xiaowei; La, Jun-Ho; Davis, Brian M.; Albers, Kathryn M.; Gebhart, G. F.

In: Gastroenterology, Vol. 140, No. 4, 04.2011, p. 1283-1291.

Research output: Contribution to journalArticle

Schwartz, ES, Christianson, JA, Chen, X, La, J-H, Davis, BM, Albers, KM & Gebhart, GF 2011, 'Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation', Gastroenterology, vol. 140, no. 4, pp. 1283-1291. https://doi.org/10.1053/j.gastro.2010.12.033
Schwartz ES, Christianson JA, Chen X, La J-H, Davis BM, Albers KM et al. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology. 2011 Apr;140(4):1283-1291. https://doi.org/10.1053/j.gastro.2010.12.033
Schwartz, Erica S. ; Christianson, Julie A. ; Chen, Xiaowei ; La, Jun-Ho ; Davis, Brian M. ; Albers, Kathryn M. ; Gebhart, G. F. / Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. In: Gastroenterology. 2011 ; Vol. 140, No. 4. pp. 1283-1291.
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