Suppression and enhancement of the Freund's incomplete adjuvant-induced writhing reaction by sodium ascorbate in mice

We noticed that an intraperitoneal injection of Freund's incomplete adjuvant (FIA) into mice could stimulate the induction of a writhing reaction. The FIA emulsion-induced writhing reaction was found to be remarkably inhibited by preadministration of oral indomethacin, a non-steroidal anti-inflammatory and analgesic drug. The induction of the writhing reaction was also inhibited by intravenous preadministration of sodium ascorbate (SAs) in saline. In the experiments where SAs was added to FIA, it was demonstrated that SAs had dual activity of suppression and enhancement. At lower concentrations SAs functioned as a suppressor of the writhing reaction, while at concentrations higher than about 1 mg/50 microl/mouse it acted as an enhancer of the reaction. Furthermore, this writhing reaction induced by FIA+SAs emulsion was also inhibited by preadministraion of SAs itself as well as indomethacin. These results suggested that the mechanism of the writhing reaction induced by FIA was concerned with the production of prostaglandins (PGs), and SAs might be involved in regulation of the writhing reaction. In this paper, we propose a mouse writhing model induced by FIA or FIA+SAs emulsion as a novel pain model useful for assessment of analgesic and anti-inflammatory agents.