(A) Timeline for ODN injections and rat behavior protocol for BK priming of peripheral DOR antinociception.
(B) WCL from ipsilateral (ipsi-) and contralateral (contra-) DRG of rats treated with MM-ODN or GRK2 AS-ODN (*p<0.05; ns = no significance; n=3 independent trials; one-way ANOVA Bonferroni post-hoc; mean ± SEM).
(C-F) Time course for DPDPE inhibition of PGE2-induced allodynia in ipsilateral (C, mechanical; D, thermal) and contralateral (E, mechanical; F, thermal) hindpaws. Paw withdrawal readings were measured 5 min and 10 min post-intraplantar (i.pl.) injection (Vehicle or BK (25 μg), and 5 min intervals for 20 min following second i.pl. injection (co-injection DPDPE (20 μg)/PGE2 (0.3 μg) (BK-induced allodynia: Mechanical and Thermal - p***<0.005 vs. vehicle-treated groups; DPDPE inhibition of PGE2-induced allodynia: Mechanical - 20 min, *p<0.05 (MM-ODN/BK); 25 min, **p<0.01 (AS-ODN/BK), ***p<0.005 (AS-ODN/Veh, MM-ODN/BK); 30 min, *p<0.05 (AS-ODN/Veh), **p<0.01 (AS-ODN/BK, MM-ODN/BK); 35 min, ***p<0.005 (MM-ODN/BK, AS-ODN/Veh, AS-ODN/BK) vs. MM-ODN/Veh; Thermal - **p<0.01 MM-ODN/BK vs. AS-ODN/Veh; 25-35, ***p<0.005 vs. groups below baseline (BL) readings; n=6 rats per group; two-way ANOVA Bonferroni post-hoc; mean ± SEM).
(G and H) Quantified antinociceptive effect of DPDPE at 35 min for (G) mechanical and (H) thermal readings (***p<0.005; ns = no significance; n=6 rats per group; two-way ANOVA Bonferroni post-hoc; mean ± SEM).