Comparison of voiding function and nociceptive behavior in two rat models of cystitis induced by cyclophosphamide or acetone.

Aims: Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (i.p.) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats.

Methods: Female Sprague-Dawley rats were used. Cystitis was induced by i.p. injection of CYP (100 and 200 mg/kg) or intravesical instillation of acetone (10%, 30%, and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an Evans blue (EB) dye leakage technique.

Results: CYP (100 mg/kg, i.p.) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200 mg/kg, i.p.) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin-pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected.

Conclusions: These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation, and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity.