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. 2022 Feb 16;42(7):1196–1210. doi: 10.1523/JNEUROSCI.1982-21.2021

Figure 7.

Figure 7.

Role of Gαi3 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/day, i.t.) against Gαi3 mRNA, daily for 3 consecutive days. On the fourth day, ∼17 h after the third injection of ODNs, systemic AD fentanyl (A: 0.03 mg/kg, s.c.) or morphine (B: 3 mg/kg, s.c.) was injected and mechanical nociceptive threshold evaluated 1 h later. Treatment with Gαi3 AS-ODN did not affect the analgesia produced by either AD fentanyl (A) or morphine (B), measured 1 h after their administration, as observed in the Gαi3 SE-ODN-treated group (A: t(10) = 0.054; ***p = 0.96; B: t(10) = 0.51, p = 0.62, when the analgesia in the Gαi3 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 intrathecal Gαi3 AS-ODN or SE-ODN. Five days after systemic AD fentanyl and morphine, at which time the mechanical nociceptive threshold was not different from preopioid baseline levels (C: SE-ODN-treated group: t(5) = 1.38, p = 0.23; AS-ODN-treated group that received systemic AD fentanyl: t(5) = 1.06, p = 0.34; D: SE-ODN-treated group: t(5) = 2.0, p = 0.1; AS-ODN-treated group that received systemic AD morphine: t(5) = 0.72, p = 0.5, 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. In both the Gαi3 AS-ODN-treated and SE-ODN-treated groups, the prolongation of PGE2-induced hyperalgesia was present 5 d after systemic AD fentanyl and morphine (C and D, respectively; C: F(1,10) = 0.58, p = 0.46; D: F(1,10) = 0.1, p = 0.75, when the hyperalgesia in the Gαi3 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). These findings support the suggestion that Gαi3 did not play a role in analgesia and hyperalgesic priming induced by AD fentanyl or morphine (n = 6 paws/6 rats/group).