title: Oxaliplatin administration increases expression of the voltage-dependent calcium channel α2δ-1 subunit in the rat spinal cord.
abstract: Oxaliplatin is a chemotherapeutic agent that is effective against various types of cancer including colorectal cancer. Acute cold hyperalgesia is a serious side effect of oxaliplatin treatment. Although the therapeutic drug pregabalin is beneficial for preventing peripheral neuropathic pain by targeting the voltage-dependent calcium channel α2δ-1 (Cavα2δ-1) subunit, the effect of oxaliplatin-induced acute cold hypersensitivity is uncertain. To analyze the contribution of the Cavα2δ-1 subunit to the development of oxaliplatin-induced acute cold hypersensitivity, Cavα2δ-1 subunit expression in the rat spinal cord was analyzed after oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that 6 mg/kg oxaliplatin-induced cold hypersensitivity 2 and 4 days later. Oxaliplatin-induced acute cold hypersensitivity 4 days after treatment was significantly inhibited by pregabalin (50 mg/kg, p.o.). Oxaliplatin (6 mg/kg, i.p.) treatment increased the expression level of Cavα2δ-1 subunit mRNA and protein in the spinal cord 2 and 4 days after treatment. Immunohistochemistry showed that oxaliplatin increased Cavα2δ-1 subunit protein expression in superficial layers of the spinal dorsal horn 2 and 4 days after treatment. These results suggest that oxaliplatin treatment increases Cavα2δ-1 subunit expression in the superficial layers of the spinal cord and may contribute to functional peripheral acute cold hypersensitivity.
authors.affiliation: Department of Education and Research Center for Clinical Pharmacy, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Tsuboi
authors.affiliation: Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Kambe
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, 31-1 Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Department of Pharmacy, Cancer Institute Hospital, 3-10-6 Ariake, Koto-Ku, Tokyo 135-8550, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Developmental Education, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Iku
authors.initials: I
authors.lastname: Utsunomiya
authors.affiliation: Department of Medicinal Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan. Electronic address: taguchi_k@mac.com.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
mesh_terms: D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D056587:Cryopyrin-Associated Periodic Syndromes / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D000069583:Pregabalin / Q000008:administration & dosage / Q000627:therapeutic use; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D015220:Calcium Channels; D009944:Organoplatinum Compounds; C494035:voltage gated calcium channel subunit Ca alpha2delta-1, human; D000077150:Oxaliplatin; D000069583:Pregabalin
keywords: Acute cold hypersensitivity; Oxaliplatin; Pregabalin; Spinal cord; Voltage-dependent calcium channel α(2)δ-1 subunit