title: Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats.
abstract: Bortezomib, an effective anticancer drug for multiple myeloma, often causes peripheral neuropathy which is mainly characterized by numbness and painful paresthesia. Nevertheless, there is no effective strategy to escape or treat bortezomib-induced peripheral neuropathy (BIPN), because we have understood few mechanism of this side effect. In this study, we evaluated behavioral and pathological characteristics of BIPN, and investigated pharmacological efficacy of various analgesic drugs and adjuvants on mechanical allodynia induced by bortezomib treatment in rats. The repeated administration of bortezomib induced mechanical and cold allodynia. There was axonal degeneration of sciatic nerve behind these neuropathic symptoms. Furthermore, the exposure to bortezomib shortened neurite length in PC12 cells. Finally, the result of evaluation of anti-allodynic potency, oral administration of tramadol (10 mg/kg), pregabalin (3 mg/kg), duloxetine (30 mg/kg) or mexiletine (100 mg/kg), but not amitriptyline or diclofenac, transiently relieved the mechanical allodynia induced by bortezomib. These results suggest that axonal degeneration of the sciatic nerve is involved in BIPN and that some analgesic drugs and adjuvants are effective in the relief of painful neuropathy.
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawashiri
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Higuchi
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Tsutsumi
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ushio
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kaname
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shirahama
authors.affiliation: Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: n-egashi@pharm.med.kyushu-u.ac.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
mesh_terms: D060433:Administration, Ophthalmic; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001369:Axons / Q000473:pathology; D000069286:Bortezomib / Q000009:adverse effects*; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008801:Mexiletine / Q000008:administration & dosage; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D016716:PC12 Cells; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D000069583:Pregabalin / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology; D014147:Tramadol / Q000008:administration & dosage
chemical_list: D000700:Analgesics; D000970:Antineoplastic Agents; D008801:Mexiletine; D014147:Tramadol; D000069583:Pregabalin; D000069286:Bortezomib; D000068736:Duloxetine Hydrochloride
keywords: Allodynia; Bortezomib-induced neuropathy; Duloxetine; Pregabalin; Tramadol