Gabapentin Prevents Oxaliplatin-Induced Mechanical Hyperalgesia in Mice

Oxaliplatin, a platinum-based chemotherapy drug, frequently causes acute and chronic peripheral neuropathies including mechanical hyperalgesia. These adverse effects hinder anticancer therapy with the drug. In this study, we examined several drugs that might prevent oxaliplatin-induced peripheral ne...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2014/07/20, Vol.125(3), pp.292-299
Main Authors: Ohsawa, Masahiro, Otake, Saki, Murakami, Tomoyasu, Yamamoto, Shohei, Makino, Toshiaki, Ono, Hideki
Format: Article
Language:English
Subjects:
Actin Depolymerizing Factors - metabolism
Amines - administration & dosage
Amines - pharmacology
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
cofilin
Cold Temperature - adverse effects
Cyclohexanecarboxylic Acids - administration & dosage
Cyclohexanecarboxylic Acids - pharmacology
Gabapentin
gamma-Aminobutyric Acid - administration & dosage
gamma-Aminobutyric Acid - pharmacology
Hyperalgesia - chemically induced
Hyperalgesia - metabolism
Hyperalgesia - prevention & control
Injections, Intraperitoneal
Male
mechanical allodynia
Mice, Inbred Strains
neuropathic pain
Organoplatinum Compounds - administration & dosage
Organoplatinum Compounds - adverse effects
Oxaliplatin
Phosphorylation - drug effects
Spinal Cord - metabolism
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Summary:Oxaliplatin, a platinum-based chemotherapy drug, frequently causes acute and chronic peripheral neuropathies including mechanical hyperalgesia. These adverse effects hinder anticancer therapy with the drug. In this study, we examined several drugs that might prevent oxaliplatin-induced peripheral neuropathy. Single intraperitoneal (i.p.) injection of oxaliplatin (10 mg/kg) induced cold allodynia (acetone test) and mechanical hyperalgesia (von Frey test). Gabapentin, but not simvastatin and atorvastatin, prevented oxaliplatin-induced mechanical hyperalgesia without affecting cold allodynia. Moreover, oxaliplatin caused phosphorylation of cofilin protein in the spinal cord, which has been shown to be involved in the neuropathic hyperalgesia. This increased phosphorylation of cofilin was also attenuated by gabapentin treatment. These results suggest that gabapentin is useful for relieving oxaliplatin-induced mechanical hyperalgesia and that the pathogenic mechanisms of cold allodynia and mechanical hyperalgesia differ.
ISSN:1347-8613
1347-8648
DOI:10.1254/jphs.14058FP