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

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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.