Figure 5:

Chronic SNC80 administration induces limited OIH/MOH. (a) Experimental outline. Separate groups of mice were tested for hind paw or cephalic allodynia. C57BL6/J mice were treated with vehicle (0.9% NaCl, VEH), SNC80 (10 mg/kg IP), or SUMA (0.6 mg/kg IP) daily for 11 days. Baselines were measured prior to the VEH/SNC80/SUMA administration. (b) SUMA- and SNC80-treated animals had significantly lower hind paw mechanical responses relative to VEH controls. p<0.001 effect of drug, time, and interaction, two-way RM ANOVA and Holm-Sidak post-hoc analysis. n=8-12/group. (c) Male C57Bl/6J mice were treated with VEH, SUMA, or SNC80 every day for 11 days, but only tested on days 1 and 11. SUMA-treated animals had significantly lower hind paw mechanical responses on day 11, an effect not observed in VEH- or SNC80-treated mice. p<0.001 effect of drug, time, and interaction, two-way RM ANOVA and Holm-Sidak post-hoc analysis. n=8-10/group. (d) Mice were treated with VEH or SNC80 every day for 11 days, and tested on days 1 and 11 for cephalic responses. SNC80 did not induce cephalic hypersensitivity, p=0.359 effect of drug and time, two-way RM ANOVA, n=8/group. (e) Mice were treated with VEH, SUMA, or SNC80 every day for 11 days, and tested on days 1, 5 and 11 for cephalic responses. SNC80 induced cephalic hypersensitivity, but at a slower rate to sumatriptan. p<0.001 effect of drug, time, and interaction, two-way RM ANOVA and Holm-Sidak post-hoc analysis. n=8-12/group. Chronic DOR activation does not induce OIH/MOH as rapidly as sumatriptan, and this effect may be through increased associative learning.