Intravesical resiniferatoxin desensitizes rat bladder sensory fibres without causing intense noxious excitation. A c-fos study

In this study the desensitizing power of increasing concentrations of resin iferatoxin applied topically to the bladder mucosa, and the irritating prop erties of the most effective desensitizing dose, were determined with the a id of the spinal expression of the proto-oncogene c-fos. Desensitization wa s assessed by the decrease in the number of Fos-immunoreactive spinal neuro ns induced by the intravesical instillation of 1% acetic acid, when the lat ter was preceded by resiniferatoxin in concentrations between 1 and 1000 nM . Irritation, as shown by the noxious excitation of vesical sensory innerva tion, was measured by the c-fos response evoked by a single application of resiniferatoxin. As to the desensitizing power, resiniferatoxin produced a dose-dependent effect with a maximum at 100 nM, which decreased Fos-immunor eactive cell numbers to less than 10% of controls. No further decrease of c -fos activation occurred at 1000 nM. As to the irritating power, the satura tion dose of resiniferatoxin (100 nM) produced a very weak c-fos activation in lumbosacral spinal cord segments. These data show that in an effective desensitizing concentration, resiniferatoxin is virtually devoid of nocicep tive effects, in agreement with current clinical observations. (C) 1999 Els evier Science B.V. All rights reserved.