Effect of dipyrone, L-NAME and L-arginine on endotoxin-induced rat paw eddema

Paw edema was induced in male Wistar rats (200-250 g) by intraplantar (ipl) administration of 2.5 mug endotoxin (Etx). Etx, like carrageenin, produced two distinct edema formation phases, an early phase (75 min) followed by a late phase (7 h). We showed that the edema formation in the early phase was antagonized by dipyrone (80 mg/kg, ip) and indomethacin (1 mg/kg, ip) by 52 per cent and 52 per cent, respectively, and that the late phase was resistant to these drugs. These result suggest that in the early phase prostaglandins appear to be involved in the process. However, the activation of the kinin cascade leading to the release of other mediators may be involved in the increase of edema in the late phase. To test this hypothesis, we investigated whether the release of nitric oxide (NO) is involved in the mechanism of endotoxin-induced rat paw edema during the late phase, using Nw-nitro-L-arginine methyl ester (L-NAME) (50 mug, ipl) as inhibitor of NO synthase and L-arginine (1 mg, ipl) as substrate of NO synthase. The paw edema induced by Etx was inhibited by L-NAME by 56 per cent and increased by L-arginine by 81 per cent. Furthermore, L-arginine given in combination with L-NAME completely reversed the inhibitions of Etx-induced edema produced by L-NAME. These results support the hypothesis that in the late phase NO production is associated with the edema evoked by Etx.

Strain-dependent effects of morphine injected into the periaqueductal gray area of mice

Microinjection of morphine (0.31,1.25 and 5.0 *g) into the periaqueductal gray area (PAG) of C57BL/6 (C57) and DBA/2 (DBA) mice increased the pain threshold in the tail-flick test. The highest dose also caused a behavioral reaction in both strains characterized by periods of immobility laternating with explosive motor behavior. In the DBA strain, the analgesic effect was demonstrated with all doses of morphine,with in the C57 strain only the highest dose induced analgesia. DBA mice presented a decrease in activity with the lowest dose of morphine, whereas in the C57 strain, this effect was obtained only with the highest dose of morphine. These data corroborate at the PAG level the results of other studies which have shown that central and peripheral injections of morphine procedure analgesia and alter motor activity in C57 and DBA strains. They also confirm that these two strains of mice present genotype-dependent differences in sensitivity to opioids as determined after injections of morphine into the PAG