Peptide immunoreactivity and ultrastructure of rat urinary bladder nerve fibers after topical desensitization by capsaicin or resiniferatoxin

In the present study the decrease of neuropeptide containing nerve fibers and the increase in the volume threshold to reflex micturition occurring in the rat bladder after intravesical application of capsaicin or resiniferatoxin were compared. The ultrastructure of bladder terminal axons was evaluated at the moment of maximal peptide depletion and compared to that of nerve fibers after systemic capsaicin application. Adult Wistar rats were treated intravesically for 30 min with 0.5 ml of 100 nM RTX, 1 mM capsaicin or 30% ethanol in saline, the vehicle solution. Twenty-four hours and 1, 2, 3, 4 and 8 weeks later the bladders were immunostained for CGRP, SP VIP and NPY. Cystomanometric studies were performed 24 h and 1, 8, and 12 weeks after vanilloid instillation. Twenty-four hours after systemic capsaicin or intravesical capsaicin or RTX, bladders were prepared for electron microscopic (EM) observation. Intravesical capsaicin or RTX decreased, in a similar way, the number of CGRP and SP-IR (immunoreactive) fibers coursing in the muscular layer and the mucosa. IR fibers amounted to less than 20% of controls at 24 h and returned to normal levels in the eighth week. At the EM level, bladders treated with topical vanilloids did not show morphological changes in terminal axons coursing in the mucosa, In contrast, bladders from animals treated systemically with capsaicin contained numerous grossly degenerated nerve fibers. VIP and NPY-IR fibers were not affected by the treatment. Cystometrograms showed an increase of the volume threshold to reflex micturition that started at 24 h and disappeared at 12 weeks. We conclude that intravesical capsaicin or RTX were equally effective in terms of reducing the number of SP and CGRP-IR fibers and increasing the volume threshold for reflex micturition. Both changes were transient and were not associated with ultrastructural changes of the bladder nerve fibers, excluding terminal axon degeneration as the main mechanism of action of intravesical vanilloids. (C) 2000 Elsevier Science B.V. All rights reserved.