Evidence for bradykinin mediation of carrageenin-induced inflammatory pain: a study using kininogen-deficient Brown Norway Katholiek rats.
Inflammatory pain was induced following an intradermal injection of carrageenin into rat paws, and the hyperalgesia was measured in terms of withdrawal time following thermal pain stimulation of the inflamed paw. This hyperalgesia was significantly less in kininogen-deficient Brown Norway (B/N)-Katholiek rats, which also showed less swelling in carrageenin-induced paw edema, than in normal B/N-Kitasato rats at 1 approximately 4 hr after the carrageenin injection (at the early phase). However, 24 hr after the injection, hyperalgesia and the swelling volume of the kininogen-deficient rats were almost the same as those in normal rats. The bradykinin B2 receptor antagonist FR173657, (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-quinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide, attenuated the carrageenin-induced swelling and hyperalgesia of the normal rats at the early phase to almost the levels of the B/N-Katholiek rats. Pretreatment with indomethacin, a cyclooxygenase inhibitor, also inhibited the carrageenin-induced responses significantly in normal rats. These results indicate that bradykinin, acting on the B2 receptor, is the main mediator at the early phase of inflammatory pain of carrageenin edema and that prostaglandins, produced by cyclooxygenase, potentiate the effects of bradykinin.
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641, Tokyo, Japan.
Y
Y
Ikeda
A
A
Ueno
H
H
Naraba
S
S
Oh-ishi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007704:Kininogens / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; C105311:FR 173657; D007704:Kininogens; D011804:Quinolines; D002351:Carrageenan; D001920:Bradykinin; D007213:Indomethacin