Among the possible models of chemotherapy-induced peripheral neurotoxicity (CIPN), there is a quite peculiar one induced by Oxaliplatin (OIPN). OIPN is a frequent side effect of chemotherapy regimens and has a relevant medical and socio-economic impact. OIPN has no cure since underlying mechanisms are still not fully understood. OIPN consists of an acute and a chronic form. Acute OIPN is a hyperexcitability syndrome arising in nearly all patients as soon as after the 1st cycle and lasting 24-72 h after each administration: transient cold-induced paraesthesia, cramps, jaw spasms. Preclinical and clinical studies demonstrated that sodium voltage operated ion channels dysfunction underlies acute OIPN. Chronic OIPN, instead, perfectly embodies persistent axonal damage, that does not resolve after chemotherapy. Acute OIPN might correspond to an upstream event and chronic OIPN to AxD. A possible downstream element, crucial in axonal damage development, might be the sodium/calcium exchanger. In this presentation it will be highlighted how, starting from patients’ clinical phenotype, it was possible to go back to the bench side with a translational approach (neurophysiology) aiming at coming back to the bed side with a potential neuroprotectant strategy based on a sound biological rationale.