Figure 5: Terpenes produce similar antinociceptive tolerance to morphine in CIPN.

Male and female CD-1 mice had CIPN induced as in the Methods, with morphine (10 mg/kg, SC) or terpene (25–200 mg/kg, IP) injection twice daily over a 4-day protocol, with daily mechanical allodynia measurement after the morning injection. Data shown is the mean ± SEM, performed in 2–5 technical replicates for each experiment, with sample sizes noted in each graph. The data shown here is the AUC calculated from each experimental set, with all raw data shown in Figures S4-S6. The morphine data is reproduced with permission from [21]. The 200 mg/kg dose of each terpene showed a roughly similar tolerance trajectory to 10 mg/kg morphine, with perhaps a less severe drop off on day 2. Lower doses of terpene had less initial efficacy, but also appear to have had slower tolerance development.