160 Yimam et al. TABLE 1. Antihyperalgesia Activity of UP446 on Carrageenan-Induced Paw Edema in Rats % Decrease of Vehicle Mean ± SD (P-values)∗ Groups 1 hr 2 hr 4 hr 6 hr 1 hr 2 hr 4 hr 6 hr Vehicle – – – Ibuprofen (150 mg/kg) 20.3 39.8 32.6 UP446 (150 mg/kg) 37.8 39.5 30.7 – 23.8 ± 4.7 27.6 ± 5.4 30.3 ± 6.3 29.7 ± 6.3 45.1 19.0 ± 4.9 16.9 ± 6.7 20.4 ± 6.4 16.3 ± 4.8 (.02) (.0003) (.001) (.00001) 33.3 14.8 ± 9.5 16.7 ± 8.2 21.0 ± 9.7 19.8 ± 8.3 (.01) (.001) (.01) (.003) Rats (N = 12) were given intraplantar injection of carrageenan λ (100 µ l of 1% [w/v] in saline) into the plantar surface of right hind paw of sedated rats at time 0 (T = 0). Rats were treated orally with UP446 (150 mg/kg) or ibuprofen (150 mg/kg) 30 min before carrageenan inoculation. Hypersensitivity threshold was determined by subtracting 1 hr, 2 hr, 4 hr, and 6 hr individual values from their respective T0 value. Data are expressed as mean ± SD and percent reduction of vehicle. ∗P-values are shown in parentheses. in paw edema for both ibuprofen and UP446 treatment groups were statistically significant at each time point considered except ibuprofen group at 6 hr. Formalin Test Intraplantar injection of formalin (2.5%) in CD-1 mice elicited a biphasic nocicep- tive response compromising flinching, leg raising, biting, and licking of the injected paw. Though previously reported formalin test-related antipain screenings limit their nociceptive reactions for the first 40 min after formalin injections, we have plotted our observations in two time blocks, which included the duration between 20–40 min after formalin and 40–60 min after formalin. In this study, both time blocks showed greater than 50% reduction in pain perception for animals treated with single oral dose of 100 mg/kg UP446 or ibuprofen with statistical significance FIGURE 1. Effect of UP446 in carrageenan-induced paw edema: Male Wistar rats (N = 12) were given intraplantar injection of carrageenan λ (100 µ l of 1% [w/v] in saline) into the plantar surface of right hind paw of sedated rats at time 0 (T = 0). Rats were treated orally with UP446 (150 mg/kg) or ibuprofen (150 mg/kg) 30 min before carrageenan inoculation. Paw edema was measured with the use of Plethysmometer at time 0 (before carrageenan), 1 hr, 2 hr, 4 hr, and 6 hr after carrageenan. Paw edema change was determined by subtracting 1 hr, 2 hr, 4 hr, and 6 hr individual values from their respective T0 value. Data are expressed as mean ± SD. ∗P ≤ .05 vs. vehicle.