The proteinase-activated receptor 2 is involved in nociception

The proteinase-activated receptor 2 is expressed on a subset of primary aff erent neurons and may participate in the neurogenic component of inflammati on. We hypothesized that this receptor may also play a role in neuronal sen sitization and contribute to the pathogenesis of pain in inflammatory condi tions such as pancreatitis. Using a specific proteinase-activated receptor 2 activating peptide, we found evidence of such sensitization in vitro in t he form of enhanced capsaicin- and KCl-evoked release of calcitonin gene-re lated peptide, a marker for nociceptive signaling. We then demonstrated tha t injection of the proteinase-activated receptor 2 activating peptide into the pancreatic duct can activate and sensitize pancreas-specific afferent n eurons in vivo, as measured by Fos expression in the dorsal horn of the spi nal cord. These observations suggest that proteinase-activated receptor 2 c ontributes to nociceptive signaling and may provide a novel link between in flammation and pain.