Fig. 2: Morphine, kurkinorin, and kurkinol all similarly reverse paclitaxel-induced allodynia in a MOR-dependent manner but show significant tolerance with repeated treatment.
Paclitaxel (4 mg/kg) was administered on day 0, 2, 4 and 6 to induce both mechanical A and thermal D allodynia in male and female mice (pooled), which were subsequently treated with daily administration of ED50 doses of morphine, kurkinorin, or kurkinol from day 17–37. Cumulative dose response curves for each MOR agonist and calculated ED50 values (± 95% confidence intervals) for mechanical B and thermal E allodynia on day 15. Effect of pre-treatment with the MOR antagonist, β-FNA (5 mg/kg), 24 h prior to MOR agonist administration and mechanical C and thermal F allodynia testing in a separate cohort of male mice. All data are presented as mean ± SEM unless otherwise stated. n = 11–12/treatment A, B, D, E, n = 6/treatment C, F. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, compared to vehicle treatment or as indicated, two-way ANOVA. #95% confidence intervals.
