Suppression of pancreatitis-related allodynia/hyperalgesia by proteinase-activated receptor-2 in mice.
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.
Kawabata
Atsufumi
A
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
Matsunami
Maho
M
Tsutsumi
Masahiro
M
Ishiki
Tsuyoshi
T
Fukushima
Osamu
O
Sekiguchi
Fumiko
F
Kawao
Naoyuki
N
Minami
Takeshi
T
Kanke
Toru
T
Saito
Naohiro
N
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
C487404:2-furoyl-LIGRLO-amide; D000700:Analgesics; D009842:Oligopeptides; D044464:Receptor, PAR-2; D002108:Ceruletide