We modeled COMT-dependent functional pain in mice as described previously.[17 (link); 46 ; 111 ] In brief, Alzet osmotic minipumps (model 1002, Durect Corporation, Cupertino, CA, USA) were implanted subcutaneously in the intrascapular region for systemic delivery of vehicle or the COMT inhibitor OR486 (Tocris Bioscience, Bristol, UK) over 14 days at a dose sufficient to cross the blood brain barrier.[67 (link)] The OR486 was dissolved in a 5:2:3 ratio mixture of dimethyl sulfoxide: ethanol: 0.9% sterile saline and injected into the pump which was subsequently incubated overnight at 37°C in a 15mL conical tube containing sterile saline.