title: Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Hospital São João, and Faculty of Medicine of Porto, Institute of Histology and Embryology, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Dinis
authors.forename: Ana
authors.initials: A
authors.lastname: Charrua
authors.forename: António
authors.initials: A
authors.lastname: Avelino
authors.forename: Francisco
authors.initials: F
authors.lastname: Cruz
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003556:Cystitis / Q000378:metabolism*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex; D013116:Spinal Cord / Q000378:metabolism*; D001743:Urinary Bladder / Q000502:physiology*; D014554:Urination / Q000502:physiology*
chemical_list: D004224:Diterpenes; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; C024353:resiniferatoxin