THE ROLE OF BLADDER AFFERENT PATHWAYS IN BLADDER HYPERACTIVITY INDUCED BY THE INTRAVESICAL ADMINISTRATION OF NERVE GROWTH FACTOR

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Abstract
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 Aδ and C fiber afferents in the type of bladder hyperactivity induced by the intravesical administration of nerve growth factor. 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 μg./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. 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. 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 Aδ afferent neurons have a major role in nerve growth factor induced bladder hyperactivity.