Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain

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. © the japanese pharmacological society.