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Physiological and immunohistochemical characterization of cisplatin‐induced neuropathy in mice
Author(s) -
Verdú Enrique,
Vilches Jorge J.,
Rodríguez Francisco J.,
Ceballos Dolores,
Valero Antoni,
Navarro Xavier
Publication year - 1999
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(199903)22:3<329::aid-mus5>3.0.co;2-8
Subject(s) - calcitonin gene related peptide , sudomotor , vasoactive intestinal peptide , endocrinology , nociception , neuropeptide , medicine , calcitonin , peripheral neuropathy , nerve conduction velocity , immunohistochemistry , peripheral nervous system , sensory nerve , sensory system , central nervous system , biology , neuroscience , receptor , diabetes mellitus
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. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 329–340, 1999