resiniferatoxin and Urethral-Obstruction

Neuroplasticity in afferent pathways, including C-fiber bladder afferents, is believed to be one of the major causes of changes in bladder function after partial urethral obstruction. We determined if capsaicin sensitive C-fiber bladder afferents are involved in the development of pre-micturition contractions after partial urethral obstruction in the rat.. Female Wistar rats were preemptively treated with capsaicin (100 mg/kg subcutaneously) or resiniferatoxin (0.3 mg/kg subcutaneously) prior to the creation of obstruction. Before and 6 weeks after obstruction micturition profiles were compared among the 3 groups, including obstructed rats preemptively treated with capsaicin (BO/CAP) or resiniferatoxin (BO/RTX) and untreated obstructed rats (BO/-). In addition, conscious filling cystometry was performed after obstruction.. Instillation of capsaicin solutions into the eye or bladder induced significant irritative reactions in BO/- but not in BO/CAP or BO/RTX, indicating that the effect of pretreatment with capsaicin or resiniferatoxin lasted 6 weeks. Voided volume per micturition on micturition profiles was decreased after partial urethral obstruction in all 3 groups. On conscious filling cystometry a significant increase in bladder capacity, voided volume and micturition threshold pressure was noted in BO/CAP but not in BO/RTX compared with BO/-. In contrast, there was no significant change in residual volume, voiding efficiency or micturition pressure among the 3 groups. The prevalence of pre-micturition contractions was 100% in BO/CAP and BO/RTX, and 83% in BO/-.. Capsaicin sensitive C-fiber afferents are not essential to induce pre-micturition contractions but they are involved in functional alterations in bladder afferent pathways after partial urethral obstruction in rats.

Topics: Afferent Pathways; Animals; Capsaicin; Diterpenes; Female; Muscle Contraction; Muscle, Smooth; Neurotoxins; Organ Size; Rats; Rats, Wistar; Urethral Obstruction; Urinary Bladder

The urodynamic effects of intravesical resiniferatoxin and capsaicin were investigated in rats.. Continuous cystometry was performed in conscious, female Sprague-Dawley rats with and without outflow obstruction.. Intravesical instillation of resiniferatoxin facilitated micturition. The potency of the drug was approximately 1,000 times higher than that of capsaicin. Repeated instillations of resiniferatoxin for 6 consecutive days caused desensitization to resiniferatoxin. This was not found with repeated instillations of capsaicin. Capsaicin was also effective in rats with bladder hypertrophy, while resiniferatoxin was not.. The findings suggest that resiniferatoxin can induce desensitization of vanilloid receptor-mediated release of tachykinins in the rat urinary bladder and that intravesical resiniferatoxin would be an interesting alternative to intravesical capsaicin in the treatment of selected cases of bladder hypersensitivity/hyperactivity.

Topics: Administration, Intravesical; Animals; Benzamides; Capsaicin; Consciousness; Diterpenes; Female; Neurotoxins; Piperidines; Rats; Rats, Sprague-Dawley; Receptors, Tachykinin; Urethral Obstruction; Urinary Bladder; Urodynamics