Cyclophosphamide-induced cystitis in rats: involvement of capsaicin-sensitive primary afferents

The involvement of capsaicin-sensitive primary afferent neurons has been investigated in a rat model of cyclophosphamide (CYP)-induced cystitis. CYP (150 mg/kg i.p., 48 h before) was administered in both vehicle- and capsaicin-(50 mg/kg s.c., 4 days before)-treated rats. Some experiments were performed 96 h after bilateral removal of pelvic ganglia (bladder denervation). CYP produced a marked detrusor hyperreflexia which was abolished by capsaicin pretreatment. CYP produced a marked increase in bladder weight and plasma protein extravasation (PPE, measured by Evans blue leakage technique): CYP-induced PPE was reduced by bladder denervation and was aggravated by capsaicin pretreatment. PPE aggravation by capsaicin was abolished by ganglionectomy. The bladder content of calcitonin gene-related peptide, was unaffected CYP. We conclude that CYP-induced decrease in bladder capacity is entirely mediated through stimulation of capsaicin-sensitive bladder afferents. At the time chosen as end point in these experiments, capsaicin-sensitive afferents exert an antiinflammatory influence on CYP-induced cystitis.