Local RMTg morphine administration and direct RMTg GABA neuron inhibition produce antinociception. (A) Effect of systemic morphine administration on paw withdrawal latency to a thermal stimulus in vGat-cre mice expressing hM3D/KORD in the RMTg (DREADD/KORD) or controls lacking the receptors (Control). Mean (±95% CI). (B) Effect of local RMTg morphine administration (1 μg/50 nL/side) or saline on paw withdrawal latency to a thermal stimulus. Mean (±95% CI), * P = 0.0004, 2-way ANOVA (see also Fig. S2 available online as supplemental digital content at http://links.lww.com/PAIN/A842). (C) Effect of intraperitoneal (i.p.) salvinorin-B (SB) and clozapine-N-oxide (CNO) on paw withdrawal latency to a thermal stimulus in vGat-cre mice expressing hM3D/KORD in the RMTg (DREADD/KORD) or controls lacking the receptors (Control). Mean (±95% CI), *P < 0.001, 2-way ANOVA. (D) Effect of i.p. SB on morphine antinociception in vGat-cre mice expressing hM3D/KORD (DREADD/KORD) or controls lacking the receptors (Control). Mean (±95% CI), *P < 0.01, t tests with the Holm–Sidak correction. (E) Effect of i.p. CNO on morphine antinociception in the same mice as (D). Mean (±95% CI), *P < 0.05, t tests with the Holm–Sidak correction. CI, confidence interval; RMTg, rostromedial tegmental nucleus.