Plasticity in the mesenteric afferent response to cisplatin following vagotomy in the rat

The aim of this study was to investigate the actions of the cytotoxic drug cisplatin on populations of mesenteric afferents supplying the rat jejunum. Extracellular whole mesenteric nerve discharge was monitored and the activ ity of individual single afferent units determined using waveform discrimin ator software. Baseline whole nerve discharge was 21.5 +/- 3.8 impulses s(- 1). Nerve discharge began to increase approximately 10 min after cisplatin administration, reached a plateau around 30 min, and remained elevated at 6 0 min (35.3 +/- 5.7 impulses s(-1), p < 0.01). Granisetron reversed the inc rease in nerve activity indicating that the response to cisplatin was media ted by the release of endogenous 5-HT acting on 5-HT3 receptors. Single aff erent units, selected by waveform analysis on the basis of their response t o exogenous 5-HT, showed a similar time course of activation following cisp latin. In contrast, the discharge frequency of afferent units that were ins ensitive to 5-HT was unaffected by cisplatin or granisetron. The sensitivit y of mesenteric afferent bundles to exogenous 5-HT was absent in chronicall y vagotomized animals. However, cisplatin elicited an increase in nerve dis charge in vagotomized animals that was not different from control (34.6 +/- 8.9 impulses s(-1)) but this increase was unaffected by treatment with gra nisetron. Thus, after vagotomy there is a switch from 5-HT3 mediated activa tion of vagal afferents to a 5-HT3-independent activation of non-vagal (pos sibly splanchnic) afferents. Since this later mechanism of activation is ab sent in control animals, it appears that there is plasticity in the gastroi ntestinal afferent sensitivity to cisplatin. (C) 1999 Elsevier Science B.V. All rights reserved.