Fig. 2.
Ligand-dependent effects of the DOR antagonist naltrindole (NTI) on dose–response curves for the KOR agonists (A) ICI-199441 and (B) U50488 for inhibition of PGE2-stimulated thermal allodynia. Rats received intraplantar injection of NTI (40 μg) 15 minutes before intraplantar injection of PGE2 (0.3 μg) along with either ICI-199441 or U50488 at the indicated doses. Data are expressed as the change in seconds from individual baseline preinjection values 10 minutes after PGE2 ± opioid agonist administration and represent the mean ± S.E.M. of six to nine animals per group. In the presence of NTI, the ICI-199441 curve was shifted significantly to the left (F(1,75) = 9.849; P = 0.0024). By contrast, the curve for U50488 was not altered by NTI (F(1,59) = .8098; P = 0.37). Injection of NTI alone had no effect on baseline PWL (F(1,40) = 1.299, P = 0.27) or on PGE2–evoked thermal allodynia (F(1,52) = 0.109; P = 0.74). As shown in Supplemental Fig. 3, injection of 40 μg NTI completely blocked a maximal dose of DPDPE for inhibition of PGE2-induced thermal nociception. Full time-course curves are presented in Supplemental Figs. 4 and 5. Veh, vehicle.