Intraepidermal innervation and tail nerve conduction velocity in neurotoxicity models: results of a correlation study in normal and pathological conditions

Animal models of human diseases affecting the peripheral nervous system are widely used to assess the pathogenesis of neurotoxicity and to compare the effect of new agents. Several behavioural, pathological and neurophysiological methods have been used, and each has advantages and disadvantages. A major goal in the study of neurotoxicity would be to assess the damage in the same way in animal models and in humans. In this study we correlated the neurophysiological results obtained in normal rats and in rats treated with cisplatin 2 mg/kg q3d × 8 with the density of intraepidermal fibers (IEF) obtained in skin biopsy specimens. The aim was to investigate the possible role of a minimally invasive procedure such as skin biopsy as an alternative method to assess the peripheral neurotoxicity of antineoplastic drugs. The nerve conduction velocity (NCV) in the tail nerve was assessed in thirty-six young adult female Wistar rats which were left untreated, or treated with erythropoietin (EPO), cisplatin (CDDP) or EPO + CDDP. CDDP and CDDP + EPO-treated rats had a significantly reduced NCV vs. age-matched untreated rats. At sacrifice, skin specimens were obtained. The density of IEF was calculated by 2 independent blinded examiners and the correlation existing between NCV and IEF was highly significant (r = 0.670, p < 0.001). This preliminary result suggests that IEF should be evaluated in other animal models and might represent a useful tool to study peripheral neurotoxicity also in humans.