Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders

BJU Int. 2004 Jul;94(1):153-7. doi: 10.1111/j.1464-4096.2004.04855.x.

Abstract

Objective: To evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation.

Materials and methods: Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined.

Results: The mean (SD) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003).

Conclusion: Intravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Cystitis / metabolism*
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacology*
  • Female
  • Neurotoxins / administration & dosage
  • Neurotoxins / pharmacology*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Wistar
  • Reflex
  • Spinal Cord / metabolism*
  • Urinary Bladder / physiology*
  • Urination / physiology*

Substances

  • Diterpenes
  • Neurotoxins
  • Proto-Oncogene Proteins c-fos
  • resiniferatoxin