title: Gabapentin and pregabalin inhibit the itch-associated response induced by the repeated application of oxazolone in mice.
abstract: We investigated the effects of gabapentin and pregabalin on the itch-associated response in a mouse model of chronic dermatitis induced by the repeated application of 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (oxazolone). Challenging the mice with oxazolone-induced chronic dermatitis with the oxazolone evoked severe and transient scratching behavior until 1 h after the application of oxazolone. Thereafter, a more mild and continuous scratching behavior was also observed for at least 8 h. Both severe and continuous scratching behaviors were suppressed by systemic injection of gabapentin and pregabalin. This effect of these compounds was correlated with its affinity for the α₂δ subunit of voltage-gated Ca²(+) channels. Intrathecal injection, but not peripheral treatment, with gabapentin inhibited the scratching behavior in this model. Gabapentin failed to suppress the scratching behavior induced by the intradermal injection of compound 48/80 in normal mice. The expression of the α₂δ-1 subunit in dorsal root ganglion (DRG) from mice following repeated application of oxazolone was significantly higher than that from normal mice. These results suggest that gabapentin and pregabalin show an anti-pruritic activity through α₂δ-subunit binding, and the up-regulation of the α₂δ-1 subunit in DRG may therefore play an important role in its anti-pruritic activity.
authors.affiliation: Kyowa Hakko Kirin Co., Ltd., Japan. yukihito.tsukumo@kyowa-kirin.co.jp
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Tsukumo
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yano
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Manabe
mesh_terms: D000588:Amines / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels; D002908:Chronic Disease; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D003875:Drug Eruptions / Q000150:complications / Q000188:drug therapy*; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors; D015854:Up-Regulation; D014581:Urticaria / Q000188:drug therapy* / Q000209:etiology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000588:Amines; C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D010081:Oxazolone; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin