Ikeda Y, Ueno A, Naraba H, Oh-ishi S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641, Tokyo, Japan.
Biochem Pharmacol. 2001 Apr 1;61(7):911-4. doi: 10.1016/s0006-2952(01)00536-6.
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.
将角叉菜胶皮内注射到大鼠爪中可诱发炎性疼痛，通过测量炎性爪受到热痛刺激后的缩足时间来评估痛觉过敏。在角叉菜胶注射后1至4小时（早期阶段），激肽原缺陷的棕色挪威（B/N）-天主教大鼠的这种痛觉过敏明显低于正常的B/N-北里大鼠，且角叉菜胶诱发的爪肿胀也较小。然而，注射后24小时，激肽原缺陷大鼠的痛觉过敏和肿胀程度与正常大鼠几乎相同。缓激肽B2受体拮抗剂FR173657，即（E）-3-（6-乙酰氨基-3-吡啶基）-N-[N-[2,4-二氯-3-[(2-甲基-8-喹啉基)氧甲基]苯基]-N-甲基氨基羰基甲基]丙烯酰胺，可将正常大鼠早期角叉菜胶诱发的肿胀和痛觉过敏减轻至几乎与B/N-天主教大鼠相同的水平。用环氧化酶抑制剂吲哚美辛预处理也可显著抑制正常大鼠角叉菜胶诱发的反应。这些结果表明，作用于B2受体的缓激肽是角叉菜胶水肿炎性疼痛早期的主要介质，且环氧化酶产生的前列腺素可增强缓激肽的作用。
