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Vincristine, a widely used antineoplastic agent, is known to be neurotoxic and to lead to chemotherapy-induced peripheral neuropathy (CIPN), which is characterized by nerve damage. Growing evidence suggests that disruption of intracellular calcium homeostasis in peripheral neurons contributes largely to the pathological conditions of CIPN. Our previous study showed that forced expression of a peripheral nerve injury-induced small heat shock protein (Hsp), Hsp27, accelerates axon regeneration and functional recovery. In the current study, we examined whether neuronal expression of human Hsp27 (hHsp27) can prevent the inhibitory effects of vincristine in two mouse models of peripheral nerve injury, namely, sciatic nerve crush and CIPN.