Fig. 3

Chronic MAGL inhibition caused no change in baseline mechanical threshold and continued to block acute migraine-associated pain in male and female C57BL6/J mice. (A) Schematic of paradigm– mice were treated with chronic MAGL inhibitor (ABD-1970 (10 mg/kg, 5x QD, PO) or methylcellulose vehicle control (PO)) every day for four days (filled in teal circle). On day 5 baselines were taken, and then animals were injected with Veh, ABD-1970, sumatriptan, or olcegepant before taking post-drug thresholds (open circle). (B) On day 5, baselines were taken (n = 8/group). 2-way repeated measures ANOVA analysis showed no significant effect of time (p = 0.8225), treatment (p = 0.2736) or interaction (p = 0.2826) after chronic MAGL inhibition. (C) Then mice were injected with ABD-1970 (10 mg/kg PO), methylcellulose vehicle control (PO) or olcegepant (1 mg/kg IP) 4 h before testing. NTG or saline vehicle (10 mg/kg IP) was administered 2 h before testing, and sumatriptan (0.6 mg/kg IP) 45 min before testing post-drug thresholds (n = 8/group). 1-way ANOVA analysis, significant effect of treatment (p < 0.001). Holm-Sidak multiple comparisons: *p < 0.05, **p < 0.01, ***p < 0.001 relative to NTG-Veh, ##p < 0.01 relative to Veh-Veh. Female animals indicated with open circles. All data are presented as mean ± SEM