Resiniferatoxin-induced loss of vanilloid receptors is reversible in the urinary bladder but not in the spinal cord of the rat.

Resiniferatoxin (RTX) induced a dose-dependent loss of vanilloid receptors (specific [3H]RTX-binding sites) in tissues containing peripheral (urinary bladder) and central (spinal cord) endings of capsaicin-sensitive neurons. This receptor loss in the spinal cord was entirely due to a reduction in the Bmax. When examined 24 h after s.c. RTX treatment, receptor loss required somewhat less RTX in the urinary bladder (ED50 = 10 micrograms/kg) than in the spinal cord (ED50 = 50 micrograms/kg), whereas the loss of the xylene-induced neurogenic inflammatory response in the bladder displayed an approximate ED50 of 5 micrograms/kg. In the bladder of rats pretreated with 30 micrograms/kg RTX, both receptor binding and neurogenic inflammatory response recovered almost completely within 2 month after treatment. In the bladder of rats that received a 10-fold higher RTX dose, a 50% recovery of binding and a 70% recovery of the Evans' blue extravasation response were found. By contrast, no recovery of specific [3H]RTX binding to spinal cord membranes was observed at either dose. These findings suggest that vanilloid receptor loss after RTX treatment can be either reversible (desensitization) or irreversible (most likely reflecting neurotoxicity), and that peripheral and central terminals of capsaicin-sensitive neurons have a differential sensitivity to these long-term vanilloid actions.