Fig. 2

Chronic treatment with morphine prevents activation-induced desensitization of TRPM8. a Top, illustration representing the experimental paradigm of morphine treatment in mice as in Fig. 1. Bottom, representative calcium imaging traces to two repeated applications of cold (20 °C, blue) or menthol (100 μM, green) in DRG neurons isolated from saline- (light color) and morphine- (MS; dark color) treated mice. b Whisker plots showing the mean ratio (R2/R1) of the amplitude response to cold stimulation in control (69.65 ± 3.2%; light blue) vs morphine (95.85 ± 4.96%; dark blue) treated mice (n = 33 and 33, respectively) or menthol stimulation in control (40.57 ± 4.44%; light green) vs morphine (88.25 ± 5.09%, dark green) treated mice (n = 30 and 33, respectively). c Percentage of responding neurons, out of all recorded neurons, to the first application of cold (3.06 ± 0.71% [36/1200] in control (light blue) vs 16.71 ± 2.68% [326/1916] after morphine (dark blue); n = 7 and 5 independent experiments, respectively) or menthol (3.31 ± 0.44% [37/1138] in control (light green) vs 16.95 ± 2.05% [32/1916] after morphine (dark green), n = 4 and 8 independent experiments, respectively). Error bars indicate ±SEM. Statistical analysis was performed using the Kruskal-Wallis ANOVA (b) or One-Way ANOVA followed by Bonferroni post hoc test (**p < 0.05)