A new writhing model of factor XII activator-induced pain for assessment of non-steroidal anti-inflammatory agents. I. Kaolin-induced writhing in mice.
The writhing reaction in mice induced by kaolin, a factor XII activator, was studied. An intraperitoneal injection of kaolin clearly induced a writhing reaction in a dose-dependent fashion, and the reaction disappeared about 10-15 min later. The writhing reaction reached a peak at 5-10 min after the injection of kaolin (0.5 ml/mouse, i.p.; 5 mg/ml saline). A simultaneous intraperitoneal injection of soybean trypsin inhibitor (SBTI, 2.5 mg/mouse) almost completely suppressed the writhing reaction caused by kaolin (2.5 mg/mouse) for the first 10 min. The kaolin-induced writhing reaction was markedly potentiated by a simultaneous intraperitoneal injection of captopril (50 micrograms/mouse). At 60 min after kaolin injection during the disappearance of the writhing reaction, the reaction reappeared when captopril was injected, but reactions observed at this later stage were completely blocked by SBTI. Indomethacin, ibuprofen and alminoprofen inhibited the writhing reaction dose-dependently. Kaolin thus induces a clear and reproducible writing reaction, which might be mainly dependent on the action of bradykinin via activation of factor XII, and should prove to be a simple and convenient model of bradykinin-induced pain for the assessment of analgesic actions.
Fujiyoshi
T
T
Pharmaceuticals Research Laboratories, Fujirebio Inc., Tokyo, Japan.
Kuwashima
M
M
Iida
H
H
Uematsu
T
T
D000109:Acetylcholine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002216:Captopril / Q000494:pharmacology; D004357:Drug Synergism; D007052:Ibuprofen / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D007616:Kaolin; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy; D010147:Pain Measurement / Q000379:methods*; D011422:Propionates / Q000627:therapeutic use; D013025:Glycine max; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D014361:Trypsin Inhibitors; C027953:alminoprofen; D007616:Kaolin; D002216:Captopril; D000109:Acetylcholine; D007052:Ibuprofen; D007213:Indomethacin