The monoacylglycerol lipase inhibitor KML29 with gabapentin synergistically produces analgesia in mice.

Gabapentin is commonly prescribed for nerve pain but may also cause dizziness, sedation and gait disturbances. Similarly, inhibition of the endogenous cannabinoid enzyme monoacylglycerol lipase (MAGL) has antinociceptive and anti-inflammatory properties but also induces sedation in mice at high doses. To limit these side effects, the present study investigated the analgesic effects of coadministering a MAGL inhibitor with gabapentin. Mice subjected to the chronic constriction injury model of neuropathic pain were administered the MAGL inhibitor KML29 (1-40 mg·kg The combination of low-dose KML29:gabapentin additively attenuated mechanical allodynia and synergistically reduced cold allodynia. The CB These data support the strategy of combining MAGL inhibition with a commonly prescribed analgesic as a therapeutic approach for attenuating neuropathic pain.