Contribution of TRPA1 as a Downstream Signal of Proteinase-Activated Receptor-2 to Pancreatic Pain

• Main Authors: Yuka Terada, Mayuko Fujimura, Sachiyo Nishimura, Maho Tsubota, Fumiko Sekiguchi, Hiroyuki Nishikawa, Atsufumi Kawabata
• Format: Article
• Language: English
• Published: Elsevier 2013-01-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S134786131930252X

We examined if TRPA1, like TRPV1, contributes to pancreatic nociceptor excitation following proteinase-activated receptor-2 (PAR2) stimulation and to pancreatitis-related pain in mice. A PAR2-activating peptide, infused into the pancreatic duct, caused spinal Fos expression, which was prevented by AP18, a TRPA1 inhibitor. Repeated administration of cerulein caused referred hyperalgesia accompanying pancreatitis, which was reversed by SB366791, a TRPV1 inhibitor, but not AP18. AP18, administered in combination with a subeffective dose of SB366791, significantly suppressed the referred hyperalgesia. Our findings suggest that TRPA1, like TRPV1, mediates PAR2-triggered pancreatic nociception and that TRPA1 in collaboration with TRPV1 latently contributes to pancreatitis-related pain. Keywords:: transient receptor potential ankyrin-1 (TRPA1), proteinase-activated receptor-2 (PAR2), pancreatic pain