RRC ID 68085
Author Yamamoto S, Kawashiri T, Higuchi H, Tsutsumi K, Ushio S, Kaname T, Shirahama M, Egashira N.
Title Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats.
Journal J Pharmacol Sci
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.
Volume 129(1)
Pages 43-50
Published 2015-9-1
DOI 10.1016/j.jphs.2015.08.006
PII S1347-8613(15)00181-4
PMID 26362518
MeSH Administration, Ophthalmic Analgesics / administration & dosage Animals Antineoplastic Agents / adverse effects* Axons / pathology Bortezomib / adverse effects* Duloxetine Hydrochloride / administration & dosage Hyperalgesia / chemically induced Hyperalgesia / drug therapy Mexiletine / administration & dosage Nerve Degeneration / chemically induced Nerve Degeneration / pathology Neurites / drug effects Neurites / pathology PC12 Cells Peripheral Nervous System Diseases / chemically induced* Peripheral Nervous System Diseases / drug therapy Peripheral Nervous System Diseases / pathology Pregabalin / administration & dosage Rats Rats, Sprague-Dawley Sciatic Nerve / pathology Tramadol / administration & dosage
IF 2.835
Human and Animal Cells PC-12(RCB0009)