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.
Maggi
C A
CA
Pharmacol. Department, A Menarini Pharmaceuticals, Florence, Italy.
Lecci
A
A
Santicioli
P
P
Del Bianco
E
E
Giuliani
S
S
D000818:Animals; D001798:Blood Proteins / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000633:toxicity*; D003556:Cystitis / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects
D001798:Blood Proteins; D003520:Cyclophosphamide; D002211:Capsaicin