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

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      European Journal of Pharmacology
      Elsevier BV

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          Abstract

          In this study the desensitizing power of increasing concentrations of resiniferatoxin applied topically to the bladder mucosa, and the irritating properties of the most effective desensitizing dose, were determined with the aid of the spinal expression of the proto-oncogene c-fos. Desensitization was assessed by the decrease in the number of Fos-immunoreactive spinal neurons induced by the intravesical instillation of 1% acetic acid, when the latter was preceded by resiniferatoxin in concentrations between 1 and 1000 nM. Irritation, as shown by the noxious excitation of vesical sensory innervation, 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-immunoreactive 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 saturation 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 nociceptive effects, in agreement with current clinical observations.

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          Author and article information

          Journal
          European Journal of Pharmacology
          European Journal of Pharmacology
          Elsevier BV
          00142999
          July 1999
          July 1999
          : 378
          : 1
          : 17-22
          Article
          10.1016/S0014-2999(99)00451-3
          10478560
          d3c3f542-08d8-4482-bd2a-ea0fe231973d
          © 1999

          https://www.elsevier.com/tdm/userlicense/1.0/

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