Gabapentin Prevents Oxaliplatin-Induced Mechanical Hyperalgesia in Mice

• 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
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.14058FP

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.