Journal
NEUROSCIENCE LETTERS
Volume 505, Issue 3, Pages 223-227Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.09.013
Keywords
Cisplatin; Peripheral neuropathy; Kv7 channel; Retigabine; Neuroprotection
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Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of many commonly used chemotherapeutic agents. One mechanism underlying this neuronal damage is via drug-induced membrane depolarization. Accordingly, one potential approach for preventing chemotherapy-induced neuropathy is via the forced maintenance of normal membrane potential during exposure to the toxic drug. More specifically, intentional elevation of the slow K+ current, via activation of Kv7 channels with a resultant hyperpolarizing shift, could be theoretically neuroprotective. In this study, in vivo nerve excitability testing in sensory nerves in mice was used to evaluate the potential therapeutic role of retigabine, a Kv7 channel activator, in the prevention of cisplatin-induced neurodegeneration. It was found that cisplatin caused membrane depolarization and peripheral axon loss that were partially prevented by retigabine pretreatment. These results support the general concept that chemotherapy-induced neuropathy can be partially inhibited via Kv7 channel activation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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