P-glycoprotein inhibitors improve effective dose and time of pregabalin to inhibit intermittent cold stress-induced central pain

Pregabalin (pgb) is a valuable therapeutic drug against chronic pain. here we attempted to perform the combinatorial drug therapy with p-glycoprotein (p-gp) inhibitors to lower therapeutic dosage of pgb in the intermittent cold stress-induced fibromyalgia-like pain model. single intracerebroventricular (i.c.v.) pgb injection exerted long-lasting anti-hyperalgesic effects for 72 h,while the effect of pgb given intraperitoneally (i.p.) disappeared within 3 h. importantly,the pretreatment with p-gp inhibitors markedly prolonged the pgb (i.p.) effects,which lasted for 72 h. these results suggest that the combinatorial treatment with p-gp inhibitor enables the prolongation of dose-interval for pgb. © 2016 the authors.