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: Contribution to journalArticle

23 被引用数 (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.

本文言語英語
ページ(範囲)43-50
ページ数8
ジャーナルJournal of Pharmacological Sciences
129
1
DOI
出版ステータス出版済み - 10 9 2015

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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