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. 2020 Jul 21;14:765. doi: 10.3389/fnins.2020.00765

FIGURE 3.

FIGURE 3

Antinociceptive effects of KOPr agonists in acute thermal pain-related behavioral models. (A) Cumulative dose-response effects of 16-Ethynyl SalA and 16-Bromo SalA in the warm water (50°C) tail-withdrawal assay. The maximal possible effect (%MPE) at each dose was calculated as a percentage based on the pre-treatment baseline latencies. Non-linear regression analysis showed 16-Ethynyl SalA and 16-Bromo SalA both exerted antinociceptive effects (n = 6). (B,C) The warm water (50°C) tail-withdrawal latencies were measured over a time course, up to 120 min (n = 7). (B) 16-Ethynyl SalA showed a significant effect up to 15 min for the 1 mg/kg dose and 60 min for the 2 mg/kg dose. (C) 16-Bromo SalA showed a significant duration of action for up to 60 min. (D) The %MPE of the paw withdrawal time on the hot-plate (50°C) was calculated based on pre-treatment baseline latencies (n = 6). Mice were treated with either vehicle, SalA (2 mg/kg), 16-Ethynyl SalA (2 mg/kg) or 16-Bromo SalA (2 mg/kg) and the withdrawal latencies measured up to 60 min. All compounds had a duration of action of 30 min, and 16-Ethynl SalA was more potent than SalA and 16-Bromo SalA at the 30 min time point. Two-way repeated-measures ANOVA followed by Bonferroni post-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 for 2 mg/kg doses vs. vehicle control. #p < 0.05, ##p < 0.01, ###p < 0.001, ####p < 0.0001 for 1 mg/kg doses vs. vehicle control. ∧∧∧p < 0.001 for 16-Ethynyl SalA vs. both SalA and 16-Bromo SalA. Values presented as mean ± SEM.