title: Suppression of pancreatitis-related allodynia/hyperalgesia by proteinase-activated receptor-2 in mice.
abstract: 1 Proteinase-activated receptor-2 (PAR2), a receptor activated by trypsin and tryptase, is abundantly expressed in the gastrointestinal tract including the C-fiber terminal, and might play a role in processing of visceral pain. In the present study, we examined and characterized the roles of PAR2 in pancreatitis-related abdominal hyperalgesia/allodynia in mice. 2 Caerulein, administered i.p. once, caused a small increase in abdominal sensitivity to stimulation with von Frey hairs, without causing pancreatitis, in PAR2-knockout (KO) mice, but not wild-type (WT) mice. 3 Caerulein, given hourly six times in total, caused more profound abdominal hyperalgesia/allodynia in PAR2-KO mice, as compared with WT mice, although no significant differences were detected in the severity of pancreatitis between the KO and WT animals. 4 The PAR2-activating peptide, 2-furoyl-LIGRL-NH(2), coadministered repeatedly with caerulein six times in total, abolished the caerulein-evoked abdominal hyperalgesia/allodynia in WT, but not PAR2-KO, mice. Repeated doses of 2-furoyl-LIGRL-NH(2) moderately attenuated the severity of caerulein-induced pancreatitis in WT animals. 5 Our data from experiments using PAR2-KO mice provide evidence that PAR2 functions to attenuate pancreatitis-related abdominal hyperalgesia/allodynia without affecting pancreatitis itself, although the PAR2AP applied exogenously is not only antinociceptive but also anti-inflammatory.
authors.affiliation: Division of Physiology and Pathophysiology, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan. kawabata@phar.kindai.ac.jp
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
authors.forename: Maho
authors.initials: M
authors.lastname: Matsunami
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsutsumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishiki
authors.forename: Osamu
authors.initials: O
authors.lastname: Fukushima
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kawao
authors.forename: Takeshi
authors.initials: T
authors.lastname: Minami
authors.forename: Toru
authors.initials: T
authors.lastname: Kanke
authors.forename: Naohiro
authors.initials: N
authors.lastname: Saito
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002108:Ceruletide; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014110:Touch
chemical_list: C487404:2-furoyl-LIGRLO-amide; D000700:Analgesics; D009842:Oligopeptides; D044464:Receptor, PAR-2; D002108:Ceruletide