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Figure 6. Lack of analgesic efficacy of antidepressants in Lmx1bf/f/p mice in the acute thermal pain model. A, Fluoxetine injection (20 mg/kg, i.p.) had no effect in Lmx1bf/f/p mice (n = 9) in the thermal threshold using a Hargreaves-type device, in comparison with that it elicited a strong analgesic effect in wild-type mice (n = 8) that lasted >3 h after injection. B, Amitriptyline injection (20 mg/kg, i.p.) elicited a strong analgesic effect in wild-type mice (n = 8) that lasted for 2 h after injection. The analgesic effect of amitriptyline is strongly attenuated in Lmx1bf/f/p mice (n = 9). C, Duloxetine injection (30 mg/kg, i.p.) elicited an analgesic effect in wild-type mice (n = 8) that peaked at 60 min after the injection. However, thermal threshold in Lmx1bf/f/p mice (n = 7) is not affected by duloxetine injection. For each animal, the percentage maximum possible effect (%MPE) was calculated using the following formula: [(postdrug latency predrug latency)/(cutoff time predrug latency)] x 100. *p < 0.05; **p < 0. 01, two-way ANOVA followed by Fisher's post hoc test. PWL, Paw-withdrawal latency. D, There were no obvious differences in the levels of NET protein tested by Western blot analyses in the spinal cord of Lmx1bf/f/p compared with wild-type mice (n = 4). WT, Wild type.