Fig. 2

Chronic NTG-induced cephalic allodynia is blocked by acute MAGL inhibition in male and female C57BL6/J mice. (A) Schematic of paradigm includes animals receiving vehicle or NTG (10 mg/kg IP) every other day for 9 days (open circle), with baseline mechanical responses measured on days 1, 5, 9, and 10. Animals were injected with Veh, ABD-1970, olcegepant, or SNC80 and tested (filled in teal circle). (B) Chronic NTG led to a decrease in mechanical threshold that lasted at least ~ 24–48 h after last injection. (n = 8/group). 2-way repeated measures ANOVA analysis, significant effect of time, treatment, and interaction (p < 0.001). Holm-Sidak multiple comparisons: ##p < 0.01, ###p < 0.001 relative to Veh-Veh. (C) Post-drug responses after treatment with ABD-1970 (10 mg/kg PO), methylcellulose vehicle control (PO) or olcegepant (1 mg/kg IP) 4 h before testing, and DOR agonist SNC80 (10 mg/kg IP) or saline vehicle (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 relative to NTG-Veh, ###p < 0.001 relative to Veh-Veh. Female animals indicated with open circles. All data are presented as mean ± SEM