Fig. 1

Systemic administration of 4R tobacco cembranoid reduces inflammation-induced peripheral hypersensitivity (a) Chemical structure (left panel) and 3D molecular model (right panel) of 4R-tobacco cembranoid. Oxygen, hydrogen, and carbon atoms are colored red, white, and grey, respectively. (b) Experimental timeline for acetone (cold), Hargreaves (heat) and von Frey (tactile) tests in CFA-injected and non-injected hind paws before and at different times after 4R (1, 6 and 15 mg/kg) or vehicle administration. (c) Acetone response score, (d) withdrawal latency to heat stimulation (e) withdrawal threshold to tactile stimulation. All values are expressed as mean ± SEM. n = 4–9 animals per treatment and test. Two-way ANOVA followed by posthoc Tukey’s multiple comparisons test: CFA-injected paw vs uninjected paw in pre-drug vehicle (veh) conditions, p < 0.0001 (####), 4R treated CFA-injected paw vs vehicle uninjected paw, p < 0.0001 (¶ ¶ ¶ ¶); not significant = ns. Two-way ANOVA followed by post hoc Dunnett’s multiple comparisons test: CFA-injected paws in vehicle vs 4R systemic treatment of the same time-point, p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), p < 0.0001 (****). Wilcoxon matched-pairs signed rank test: CFA-injected paw vs uninjected paw in pre-drug vehicle (veh) conditions, p < 0.01 (††), Non-parametric Mann–Whitney multiple comparisons test followed by Holm-Šídák method; CFA-injected paws in vehicle vs 4R systemic treatment of the same time-point, adjusted p < 0.01 (‡‡), adjusted p < 0.001 (‡‡‡); vehicle (veh) uninjected paw (day 7) vs 4R 15 mg/kg CFA-injected paw (day 7), adjusted p > 0.05 (§§). Results of multiple comparisons between vehicle (veh) and 4R 1 mg/kg, 6 mg/kg or 15 mg/kg are shown in purple, teal, and orange, respectively