Involvement of Prostaglandins in Kaolin-Induced Writhing Reaction in Mice

抄録

The relationship between the kaolin-induced writhing reaction and production of arachidonate metabolites (PGs) in mice was studied. PGs were released into the peritoneal cavity after intraperitoneal injection (i.p.) of kaolin (2.5 mg/mouse) with a peak at 5 min. About 80% of the total amount was 6-keto-PGF_1α. There was a significant correlation (r=0.8237, p<0.001) between the number of writhes and the amount of 6-keto-PGF_1α. The writhing reaction induced by kaolin was significantly inhibited by simultaneous injection of soybean trypsin inhibitor (SBTI ; 2.5 mg/mouse) and increased by simultaneous injection of captopril (50μg/mouse). The writhing reaction induced by kaolin which was inhibited by oral administration of indomethacin (1 mg/kg) was restored by exogenous i.p. injection of PGI₂-Na (2-10ng/mouse). Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction and reduced the level of peritoneal 6-keto-PGF_1α in parallel manner. Tiaramide, pentazocine and morphine inhibited the writhing reaction without reducing the revels of 6-keto-PGF_1α. These results differentiate the site of action of these analgesics. They suggest that the mechanism of the kaolininduced writhing reaction in mice involves a synergic pain caused by simultaneously released bradykinin and PGI₂. This model is a useful tool which allows differentiation of mode of action of analgesics by simultaneous determination of the writhing response and peritoneal 6-keto-PGF_1α.