Physiological and immunohistochemical characterization of cisplatin- induced neuropathy in mice

Enrique Verdú, Jorge J. Vilches, Francisco J. Rodríguez, Dolores Ceballos, Antoni Valero, Xavier Navarro

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    76 Citations (Scopus)

    Abstract

    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 nerve 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 immunohistochemically localized in footpads. Tibial nerves were analyzed morphometrically. Functional deficits developed progressively with higher cumulative doses, more markedly in mice treated with high than in those with low doses. From cumulative doses of 10 mg/kg, significant declines in sensory nerve conduction velocity and sudomotor responses were found, whereas motor and nociceptive functions were involved later. There were no morphometrical changes in tibial nerves. A marked decrease of CGRP- and VIP- immunoreactive nerves occurred in samples from treated mice, whereas PGP- labeled profiles decreased mildly at late stages. Impairment of the content of neuropeptides with neurosecretor role was detectable earlier than functional abnormalities. Immunohistochemical analysis of skin biopsies offers a useful diagnostic tool for peripheral neuropathies.
    Original languageEnglish
    Pages (from-to)329-340
    JournalMuscle and Nerve
    Volume22
    Issue number3
    DOIs
    Publication statusPublished - 16 Mar 1999

    Keywords

    • Cisplatin
    • Electrophysiology
    • Immunohistochemistry
    • Motor function sensory function
    • Neuropathy
    • Skin
    • Sudomotor

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