Involvement of NGF in the induction of increased noradrenergic innervation of the ureter in neonatally capsaicin-treated rats

Neonatal denervation of primary afferents with capsaicin leads to increased sympathetic innervation of the rat ureter. In the present study the development and the immunohistochemical characterization of this sympathetic hyperinnervation as well as the specific involvement of nerve growth factor (NGF) was investigated. Noradrenaline levels were found elevated in neonatally capsaicin-treated rats by 2 weeks of age and remained at that high level into adulthood. Injections of an anti-NGF antiserum during postnatal days (PN) PN 8-14, PN 13-19 or during PN 17-23 counteracted the capsaicin effect and reduced noradrenaline towards control levels. Immunohistochemical localization of tyrosine hydroxylase (TH), a marker for sympathetic nerve fibres, revealed that the capsaicin-induced hyperinnervation was mainly represented by fibres in deeper muscle layers and to a smaller extent by fibres in the submucosa. In control animals and in rats treated with capsaicin and anti-NGF antiserum fibres were mainly distributed in the adventitia and in the outer part of the smooth muscle layer. These results show that NGF is responsible for the development of an increased noradrenergic innervation in the rat ureter after neonatal capsaicin treatment. (C) 1998 Elsevier Science B.V. All rights reserved.