Figure 10. Slow onset STZ-induced PDN is manifested by thermal and mechanical hypersensitivity, which is abolished by AS oligonucleotides designed to knock down the gene encoding the Cav3.2 isoform of T-channels.
Panel A shows baseline BG levels (0 days) that were determined before STZ injection (50 mg/kg, i.p.; marked with arrow) and found to be within normal limits. Daily BG measures were recorded in the two groups of rats that were given either injections of STZ i.p and AS-CaV3.2 i.t. (STZ-AS, filled squares), or injections of STZ i.p. and MIS-CaV3.2 i.t. (STZ-MIS, filled circles). STZ-injected animals in both groups became severely hyperglycemic during 4-th week following injection (arrow) and remained so for at least 10 subsequent days, with BG levels ranging from 450 to 500 mg/dl.
Panels B and C show complete reversal of thermal hypersensitivity measured with PWL in diabetic rats with i.t injections of AS-CaV3.2 but not MIS-CaV3.2 (boxed area) in the right paws (filled symbols, panel B) and left paws (open symbols, panel C). Panels D and E show complete reversal of mechanical hypersensitivity measured with PWRs in diabetic rats with i.t injections of AS-CaV3.2 but not MIS-CaV3.2 (boxed area) in the right paws (filled symbols, panel D) and left paws (open symbols, panel E). n ≥ 6 animals per data point.
*, p<0.05 for baseline (day 0) vs. day 1–10 for STZ-AS;
†, p<0.05 for baseline (day 0) vs. day 1-10 for STZ-MIS;
‡, p<0.05 for day 0–10 for STZ-AS vs. STZ-MIS;