Figure 2. Rapid onset STZ-induced PDN is manifested by thermal hypersensitivity, which is abolished by AS oligonucleotides designed to knock down the gene encoding the Ca_v3.2 isoform of T-channels.

In STZ-injected animals (panel A, right paws; panel B, left paws), PWLs were obtained before i.v. STZ injection (arrow) and daily thereafter for up to 10 days. Compared to the baseline PWL, PWLs on day 3 after injection were significantly decreased in STZ-injected animals (*, p < 0.05). Intrathecal injection of AS (boxed area) starting on day 3 caused a significant increase in PWLs as compared to those of rats in the SAL and MIS treatment groups on day 5 and thereafter in both paws (†, p<0.01) (for the left paw on day 4 as well when compared to MIS group, ‡, p<0.05). In both SAL and MIS groups PWLs remain significantly decreased throughout the entire testing period in both right (A) and left (B) paws when compared to the baseline recordings (day 0) (*, p< 0.05) (n=5–10 animals per data point).

Saline-injected animals (panel C, right paws; panel D, left paws) showed no changes in PWLs on day 3 as compared to the baseline PWLs. Intrathecal injection of SAL or MIS on day 3 had no significant effect on PWLs throughout the testing period. The AS-injected group showed a significant increase in PWLs on the right side on days 5, 6 and 7 as compared to the MIS group (‡, p<0.05) but not SAL group. In left paw (panel D) PWLs recorded on days 6 and 7 were significantly increased compared to MIS group (‡, p<0.05) but only on day 6 when compared to SAL group (†, p< 0.05). The PWLs were also significantly higher in AS group on days 6 and 7 in both right (panel C) and left (panel D) paws as compared to their respective baseline PWLs (*, p< 0.05) (n = 5–9 animals per data point).