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 carrage enin into rat paws, and the hyperalgesia was measured in terms of withdrawa l time following thermal pain stimulation of the inflamed paw. This hyperal gesia was significantly less in kininogen-deficient Brown Norway (B/N)-Kath oliek rats, which also showed less swelling in carrageenin-induced paw edem a, than in normal B/N-Kitasato rats at 1 similar to4 hr after the carrageen in injection (at the early phase). However, 24 hr after the injection, hype ralgesia and the swelling volume of the kininogen-deficient rats were almos t the same as those in normal rats. The bradykinin B-2 receptor antagonist FR173657, (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[(2-methyl-8-q uinolinyl)oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide, attenua ted the carrageenin-induced swelling and hyperalgesia of the normal rats at the early phase to almost the levels of the B/N-Katholiek rats. Pretreatme nt with indomethacin, a cyclooxygenase inhibitor, also inhibited the carrag eenin-induced responses significantly in normal rats. These results indicat e that bradykinin, acting on the B-2 receptor, is the main mediator at the early phase of inflammatory pain of carrageenin edema and that prostaglandi ns, produced by cyclooxygenase, potentiate the effects of bradykinin. (C) 2 001 Elsevier Science Inc. All rights reserved.