Figure 3. Rapid onset STZ-induced PDN is manifested by mechanical hypersensitivity, which is alleviated by AS oligonucleotides designed to knock down the gene encoding the Cav3.2 isoform of T-channels.
PWRs on day 3 after the injection of STZ (panel A, right paws; panel B, left paws) were significantly increased (*, p < 0.05) as compared to baseline recordings. Intrathecal injection of AS (boxed area) in i.v. STZ-treated rats caused a significant decrease in PWRs in both right paws as compared to PWRs of the SAL- and MIS- treated STZ rats and remained significantly decreased (†, p < 0.05) throughout the testing period. PWRs in both paws of the SAL and MIS groups remained significantly higher as compared to the baseline recording (day 0) throughout the testing period (*, p < 0.05) while PWRs in both paws of the AS group were no different on days 5 through 7 as compared to the baseline recording (n = 5–10 animals per data point).
Saline-injected animals showed no changes in PWRs of either paw (panel C, right; panel D, left) on day 3 as compared to baseline PWRs. Intrathecal injection of SAL or MIS had no significant effect on PWRs in mechanical sensitivity throughout the testing period compared to the baseline recordings. In the AS-injected group, there was small but significant increase in PWRs on day 4 in both paws (panel C, right; panel D, left) as compared to the MIS group (‡, p < 0.05) (n=5 to 9 animals per data point).