Physiological and immunohistochemical characterization of cisplatin-induced neuropathy in mice

We investigated the neuropathic effects of cisplatin in two groups of mice treated with 5 or 10 mg/kg/week of cisplatin for 7 or 8 weeks. Peripheral n erve functions were evaluated by sweat imprints, and electrophysiological, rotarod, and nociceptive tests, Protein gene product 9.5 (PGP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were i mmunohistochemically localized in footpads. Tibial nerves were analyzed mor phometrically. Functional deficits developed progressively with higher cumu lative doses, more markedly in mice treated with high than in those with lo w doses. From cumulative doses of 10 mg/kg, significant declines in sensory nerve conduction velocity and sudomotor responses were found, whereas moto r and nociceptive functions were involved later. There were no morphometric al changes in tibial nerves. A marked decrease of CGRP- and VIP-immunoreact ive nerves occurred in samples from treated mice, whereas PGP-labeled profi les decreased mildly at late stages. Impairment of the content of neuropept ides with neurosecretor role was detectable earlier than functional abnorma lities. Immunohistochemical analysis of skin biopsies offers a useful diagn ostic tool for peripheral neuropathies. (C) 1999 John Wiley & Sons, Inc.