Figure 3. SGC-targeted DBI overexpression reduces mechanical sensitivity in naïve mice and suppresses mechanical allodynia in neuropathic and inflammatory pain models.

A, Schematic timeline for the viral DRG gene delivery and chronic pain induction experiments; inset depicts DRG 8 weeks after injection with AAV5-gfaABC1D-DBI-EGFP virions. B, RT-PCR confirmation of Dbi overexpression in the DRG; *** indicate significant difference from control group (p<0.001, unpaired t-test). C, D, Mechanical (von Frey; C) and heat (Hargreaves; D) sensitivity was monitored on the ipsilateral paws during 42 days after the DRG injection of AAV5-gfaABC1D-DBI-EGFP virions or GFP control virions (1.1 – 1.2×10¹² vg/ml; 2 μl). *** indicate significant difference from time-matched control group (p<0.001; two-way repeated-measures ANOVA with Tukey’s post-hoc test). E, F, similar to C, D, but the tests were conducted on the contralateral paws. G, H Mechanical (G) and heat (H) sensitivity was monitored after the induction of the spared nerve injury model (SNI; see Methods) to the mice pre-injected with AAV5-gfaABC1D-DBI-EGFP virions. I, J, Mechanical (I) and heat (J) sensitivity was monitored after the induction of the Complete Freund’s Adjuvant inflammatory pain model (CFA; see Methods) to the mice pre-injected with AAV5-gfaABC1D-DBI-EGFP virions. In G–J, *, **, indicate significant difference from time-matched control group (at p<0.05, or p<0.01, respectively; two-way repeated-measures ANOVA with Tukey’s post-hoc test).