Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity

Neuropathy is the dose-limiting side effect of vincristine (VCR) in cancer therapy. However, no simple experimental model has yet been reported. Here, we present a simple experimental model of VCR neurotoxicity using a mouse sciatic nerve crush model, which allows evaluation within a few weeks. VCR administered intravenously once on the day after the crush lesion caused a dose-dependent delay of the recovery of motor and sensory functions. The mi nimal dose required to cause the delay was 0.25 mg/kg, wh ich corresponded to five times the usual clinical dose for man a nd was far less than the re ported doses required to cause functional impairment in intact animals. The model would be useful not only for the development of new drugs but also f or the estimation of the drug interactions in combination cancer therapy. ( C) 2001 Elsevier Science Ireland Ltd. All rights reserved.