title: Antinociceptive Effects of the Serotonin and Noradrenaline Reuptake Inhibitors Milnacipran and Duloxetine on Vincristine-Induced Neuropathic Pain Model in Mice.
abstract: Vincristine is an anticancer drug used to treat a variety of cancer types, but it frequently causes peripheral neuropathy. Neuropathic pain is often associated with the appearance of abnormal sensory signs, such as allodynia. Milnacipran and duloxetine, serotonin/noradrenaline reuptake inhibitors, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of vincristine-induced mechanical allodynia in mice by milnacipran and duloxetine. To induce peripheral neuropathy, vincristine was administered once per day (0.1 mg/kg, intraperitoneally (i.p.)) for 7 days. Mechanical allodynia was evaluated by measuring the withdrawal response to stimulation with a von Frey filament. In vincristine-treated mice, mechanical allodynia was observed on days 3-28 of vincristine administration. A single administration of milnacipran (40 mg/kg, i.p.) or duloxetine (20 mg/kg, i.p.) had no effect on vincristine-induced mechanical allodynia. However, repeated administration of milnacipran (20 or 40 mg/kg, once per day, i.p.) or duloxetine (5, 10, or 20 mg/kg, once per day, i.p.) for 7 days significantly reduced vincristine-induced mechanical allodynia. These results suggest that chronic vincristine administration induces mechanical allodynia, and that repeated milnacipran and duloxetine administration may be an effective approach for the treatment of neuropathic pain caused by vincristine treatment for cancer.
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Soh
authors.initials: S
authors.lastname: Katsuyama
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Aso
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Otowa
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yagi
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Yukinaga
authors.initials: Y
authors.lastname: Kishikawa
authors.affiliation: Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
authors.affiliation: Department of Clinical Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Hitoshi
authors.identifier: 0000-0002-4863-1966
authors.initials: H
authors.lastname: Nakamura