Extended Data Fig. 13: Opioid analgesia mimicry via chemogenetic inhibition of nociceptive MOR + ACC neurons in acute pain.
Chemogenetic inhibition of ACC MOR+ cells (Red: mMORp-hM4, n = 15), ACC nociceptive MOR+ cells (Blue: mMORp-FlpO + CreON/FlpON-hM4 in painTRAP mice, n = 15), or control/non-inhibited (Gray: mMORp-eYFP, n = 15). (a) Reflexive withdrawal thresholds and affective-motivational response duration to noxious hot (55 °C hot water) and cold (acetone) stimuli at baseline and after administration of DCZ. (Two-way ANOVA,Tukey correction: von Frey pInteraction = 0.6451, acetone pInteraction = 0.003, hot water pInteraction <0.0001) (b) Latency to withdraw (p < 0.0001), total withdrawals (p < 0.0001), latency to attend (p < 0.0001), and total duration of attending (p < 0.0001) induced in 60 s on a 50 °C inescapable hot plate after DCZ. (One-way ANOVA, Tukey correction for all panels) (c) Duration of time between the first reflexive withdrawal and the first bout of attending behaviours on the inescapable hot plate after DCZ. (One-way ANOVA, Tukey correction, p < 0.0001) (d) The proportion of the trial engaging in attending behaviours after the first attending bout on the inescapable hot plate after DCZ. (One-way ANOVA, Tukey correction, p < 0.0001). ⋆ = p < 0.05. Barsor dots are mean; lines are individual animals; error bars are SEM. See Table S1 Rows 137–145 for statistics.
