Figure 1.

Coadministration of the selective MAGL inhibitor KML29 and gabapentin additively attenuated mechanical allodynia and synergistically reduced cold allodynia in mice subjected to CCI. A separate group of mice was subjected to CCI and then administered KML29, gabapentin or vehicle and tested for mechanical and cold allodynia. Then, KML29 was coadministered with gabapentin and mechanical (A) and cold allodynia (E) were assessed. The isobole of additivity is shown as a solid line connecting the ED₅₀ values of KML29 and gabapentin and depicting the theoretical line of additivity. The experimental points of the collective mechanical allodynia tests (B–D) do not differ significantly from line of additivity, indicating an additive interaction. The experimental points of the collective cold allodynia tests (F–H) significantly lie below the theoretical line of additivity, indicating a synergistic interaction. Data are expressed as mean (±) SEM. *P < 0.05 versus vehicle (n = 15).