title: P-glycoprotein inhibitors improve effective dose and time of pregabalin to inhibit intermittent cold stress-induced central pain.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Mukae
authors.affiliation: Department of Frontier Life Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Fujita
authors.affiliation: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: ueda@nagasaki-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy; D003080:Cold Temperature; D003524:Cyclosporins / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005356:Fibromyalgia / Q000188:drug therapy*; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000188:drug therapy; D000069583:Pregabalin / Q000627:therapeutic use*; D012584:Sciatic Nerve / Q000601:surgery
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000700:Analgesics; D003524:Cyclosporins; D000069583:Pregabalin; C070272:valspodar
keywords: Fibromyalgia; P-glycoprotein; Pregabalin