Opioid-induced DRG neuronal hyperexcitability is dependent on receptor endocytosis. A, Patch-clamp recordings show that the OPr antagonist naloxone (NLX) prevented the decrease in the rheobase evoked by high-concentration DAMGO and DADLE applied overnight (F(2,78) = 8.143, p = 0.0006, two-way ANOVA with Bonferroni's post hoc test). B, The clathrin inhibitor PS2 also prevented the decrease on the rheobase evoked by high-concentration opioids (F(1,98) = 10.63, p = 0.0015, two-way ANOVA with Bonferroni's post hoc test). C, Acute application of a weakly internalizing DOPr agonist ARM390 at equally high concentration did not alter neuron rheobase, whereas overnight incubation increased neuron rheobase (F(2,58) = 3.064, p = 0.054, one-way ANOVA with Dunnett's post hoc test). Number of cells appears in each bar. Error bars indicate mean ± SEM. *p ≤ 0.05. **p ≤ 0.01. ***p ≤ 0.001.