Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats

Shota Yamamoto, Takehiro Kawashiri, Hitomi Higuchi, Kuniaki Tsutsumi, Soichiro Ushio, Takanori Kaname, Masafumi Shirahama, Nobuaki Egashira

研究成果: ジャーナルへの寄稿記事

18 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)43-50
ページ数8
ジャーナルJournal of Pharmacological Sciences
129
発行部数1
DOI
出版物ステータス出版済み - 10 9 2015

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Peripheral Nervous System Diseases
Pharmacology
Hyperalgesia
Sciatic Nerve
Analgesics
Mexiletine
Tramadol
Amitriptyline
Hypesthesia
Bortezomib
Paresthesia
Diclofenac
PC12 Cells
Neurites
Multiple Myeloma
Oral Administration
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

これを引用

Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats. / Yamamoto, Shota; Kawashiri, Takehiro; Higuchi, Hitomi; Tsutsumi, Kuniaki; Ushio, Soichiro; Kaname, Takanori; Shirahama, Masafumi; Egashira, Nobuaki.

:: Journal of Pharmacological Sciences, 巻 129, 番号 1, 09.10.2015, p. 43-50.

研究成果: ジャーナルへの寄稿記事

Yamamoto, Shota ; Kawashiri, Takehiro ; Higuchi, Hitomi ; Tsutsumi, Kuniaki ; Ushio, Soichiro ; Kaname, Takanori ; Shirahama, Masafumi ; Egashira, Nobuaki. / Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats. :: Journal of Pharmacological Sciences. 2015 ; 巻 129, 番号 1. pp. 43-50.
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