ECN, a selective T-channel blocker and neuroactive steroid, induced greater dose-dependent alleviation of mechanical hypersensitivity
in ob/ob mice (A and B) than in wild-type (C and D) mice. All dose-response experiments were done in 10- to 12-week-old mice (at the peak of mechanical hypersensitivity). PWRs
were recorded at 90–120 min after injection of ECN (at the peak effect on thermal hypersensitivity). Intraperitoneal injection
of 5 mg/kg of ECN had no effect on PWRs in either right (A) or left paws (B) of ob/ob mice. When 10 mg/kg was given, PWRs were significantly decreased compared with those at 0 min (immediately before the injection)
(*P < 0.001) in both right (A) and left paws (B). The highest dose of ECN, 25 mg/kg, caused a profound decrease in PWRs leading to complete reversal of mechanical hypersensitivity;
that is, PWRs were similar to the baseline PWRs recorded in wild-type mice (dotted line). When 10 mg/kg of ECN was administered
to wild-type mice, there was no effect on PWRs in either right (C) or left paws (D); that is, PWRs remained at the baseline level (dotted line). At the highest dose, 25 mg/kg, ECN caused a significant decrease
in PWRs (*P < 0.001 compared with vehicle at 90–120 min) (n = 6 ob/ob mice per group; n = 5–6 wild-type mice per group). WT, wild type.