Figure 8.

Role of Gα_o in analgesia and hyperalgesic priming induced by systemic AD fentanyl and morphine. Rats received intrathecal injections of AS-ODN (120 μg in 20 μl/d, i.t.) or SE-ODN (120 μg in 20 μl/d, i.t.) against Gα_o mRNA, daily for 3 consecutive days. On the fourth day, AD fentanyl (A: 0.03 mg/kg, s.c.) or morphine (B: 3 mg/kg, s.c.) was administered and the mechanical nociceptive threshold was evaluated 1 h later. In the groups of rats treated with Gα_o AS-ODN, systemic AD fentanyl (A), and morphine (B) induced analgesia that was not different when compared with their respective Gα_o SE-ODN-treated groups (A: t₍₁₀₎ = 0.13, p = 0.90; B: t₍₁₀₎ = 0.005, p = 0.99, when the analgesia in the Gα_o AS-ODN-treated and the SE-ODN-treated groups is compared at 1 h after systemic AD fentanyl and morphine, respectively; unpaired Student's t test). At the end of the fourth day, rats again received Gα_o AS-ODN or SE-ODN. Five days after systemic AD fentanyl and morphine, when the mechanical nociceptive threshold was not different from the preopioids baselines (C: SE-ODN-treated group: t₍₅₎ = 2.03; p = 0.09; AS-ODN-treated group that received AD fentanyl: t₍₅₎ = 1.26; p = 0.26; D: SE-ODN-treated group: t₍₅₎ = 1.1, p = 0.32; AS-ODN-treated group that received AD morphine: t₍₅₎ = 1.52, p = 0.19, when the mechanical nociceptive threshold is compared before and 5 d after systemic AD opioids; paired Student's t test), PGE₂ (100 ng/5 μl, i.d.) was injected and the mechanical nociceptive threshold was evaluated 30 min and 4 h later. Treatment with Gα_o AS-ODN markedly attenuates PGE₂-induced prolonged hyperalgesia in rats that received AD fentanyl (C: F_(1,10) = 23.6, *** p = 0.0007, when the hyperalgesia in the Gα_o AS-ODN-treated and the SE-ODN-treated groups is compared at the fourth hour after intradermal PGE₂; two-way repeated-measures ANOVA followed by Bonferroni's post hoc test). However, the prolongation of PGE₂-induced hyperalgesia was not affected by treatment with Gα_o AS-ODN in the AD morphine-treated group (D: F_(1,10) = 2.89, p = 0.12, when hyperalgesia was compared between the Gα_o SE-ODN-treated and AS-ODN-treated groups at the fourth hour after intradermal PGE₂; two-way repeated-measures ANOVA followed by Bonferroni's post hoc test). These findings indicate that analgesia produced by systemic AD fentanyl and morphine is not Gα_o subunit dependent; however, the Gα_o subunit does play a role in hyperalgesic priming induced by AD fentanyl, but not morphine (n = 6 paws/6 rats/group).