The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor.
OBJECTIVE
Interstitial cystitis, a chronic disease of the bladder, is characterized by urinary frequency, urgency and suprapubic pain. Nerve growth factor is a substance that may sensitize afferent nerves and induce bladder hyperactivity. It is often increased in the urine of patients with interstitial cystitis. We evaluated the role of Adelta and C fiber afferents in the type of bladder hyperactivity induced by the intravesical administration of nerve growth factor.


METHODS
A total of 22 Wistar and 8 Sprague-Dawley adult female rats were anesthetized with 1.2 gm/kg urethane given subcutaneously. A transurethral catheter was inserted into the bladder. Some animals were pretreated with 125 mg/kg capsaicin injected subcutaneously 4 days before nerve growth factor administration. Cystometry was performed by slowly filling the bladder at a rate of 0.04 ml per minute for 15 minutes with a volume of up to 0.6 ml. Parameters measured included volume threshold and pressure threshold for inducing the micturition reflex, compliance, bladder contraction amplitude, number of contractions and the inter-contraction interval. Nerve growth factor (0.5 ml of 20 microg/ml in 10% dimethyl sulfoxide) or a vehicle solution (0.5 ml of 10% dimethyl sulfoxide) was infused into the bladder through a transurethral catheter and retained for 1 hour.


RESULTS
In Wistar rats nerve growth factor increased the mean number of contractions by 111% versus controls (5.7 versus 2.7, p <0.05), and decreased the mean volume threshold by 41% (0.244 versus 0.412 ml, p <0.05). This effect of nerve growth factor was not detected in Sprague-Dawley rats. Capsaicin pretreatment increased the volume threshold by 59% but did not change nerve growth factor induced bladder hyperactivity.


CONCLUSIONS
The intravesical application of nerve growth factor acutely induced bladder hyperactivity in Wistar but not in Sprague-Dawley rats. Because the C fiber afferent neurotoxin capsaicin did not change the effect of nerve growth factor, we believe that Adelta afferent neurons have a major role in nerve growth factor induced bladder hyperactivity.
Chuang
Y C
YC
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Fraser
M O
MO
Yu
Y
Y
Chancellor
M B
MB
de Groat
W C
WC
Yoshimura
N
N
D000283:Administration, Intravesical; D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology
D020932:Nerve Growth Factor; D002211:Capsaicin