title: Contribution of TRPA1 as a downstream signal of proteinase-activated receptor-2 to pancreatic pain.
abstract: 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.
authors.affiliation: Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Terada
authors.forename: Mayuko
authors.initials: M
authors.lastname: Fujimura
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nishimura
authors.forename: Maho
authors.initials: M
authors.lastname: Tsubota
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D059225:Nociception / Q000502:physiology; D010195:Pancreatitis / Q000150:complications*; D044464:Receptor, PAR-2 / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000813:Anilides; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D044464:Receptor, PAR-2; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse