NEUROPEPTIDES AND MORPHOLOGICAL-CHANGES IN CISPLATIN-INDUCED DORSAL-ROOT GANGLION NEURONOPATHY

Dorsal root ganglia (DRG) neuronopathy was induced in rats by chronic treatment (2 mg/kg twice a week for nine injections) with the antineop lastic drug cisplatin. Morphological alterations and changes in peptid e [calcitonin gene-related peptide (CGRP), substance P, galanin (Gal), and somatostatin] concentration were studied in the DRG, the spinal c ord, and the sciatic nerve. Peptide concentration was increased in DRG neurons, with CGRP and Gal showing the highest increase. Conversely, in the sciatic nerve there was a general decrease in peptide content. In DRG a reduction in the nuclear, cytoplasmic, and nucleolar areas of primary sensory neurons was evident and was accompanied by clear-cut aspects of nucleolar structural damage. In peripheral nerves only exte nsive morphometric determinations could evidence a reduction in large myelinated fibers. Electrophysiological and behavioral studies evidenc ed a reduction in nerve conduction velocities and impairment in pain d etection and coordination. Some of the nerve fibers presented axonal a nd adaxonal accumulations, suggesting the presence of an axonopathy. T hese results confirm that DRG cells are the primary target of cisplati n-induced neurotoxicity. Milder alterations can be detected in periphe ral nerves. The increase in peptide concentration in DRG is probably d ue to cisplatin-related damage to the axonal transport system rather t han to an increased synthesis. (C) 1996 Academic Press, Inc.