Figure 6: Terpenes evoke antinociception in CIPN via the A_2AR.

Male and female CD-1 mice had CIPN induced and measured as described in the Methods. Data shown is the mean ± SEM, performed in 2–3 technical replicates for each experiment, with sample sizes noted in each graph. BL = baseline. A) Naïve mice with no CIPN had vehicle or the A_2AR antagonist istradefylline (3.2 mg/kg, IP) injected, followed by mechanical threshold measurements. Istradefylline had no impact on naïve mechanical thresholds, validating the dose. B) CIPN mice had vehicle or istradefylline (3.2 mg/kg, IP) injected, with a 10 min treatment time, followed by terpene (200 mg/kg, IP) as noted. *, **, ***, **** = p < 0.05, 0.01, 0.001, 0.0001 vs. same time point istradefylline/terpene group by RM 2 Way ANOVA with Sidak’s post hoc test. Istradefylline significantly reduced antinociception in CIPN by each terpene, implicating the A_2AR as a mechanism of action.