Introduction and Objectives
The pivotal backgrounds for overactive bladder (OAB) development are as follow: the C-fibres sensitisation (increment of sensitivity to various stimuli acting on urotelium) and local effector function of afferent C-fibres endings leading to neurogenic inflammation. Considering the polymodal features of afferent C-fibre we explored the urodynamic effect of primary afferent neurons modulation on detrusor activity in normal and overactive bladder model rats.
Material and Methods
Experiments were performed on 48 female rats. OAB was induced by cyclophosphamide (CYP) – 75 mg/kg i.p., every 3rd day for 7 days. Animals were divided into 6 groups:
- III.OAB + capsaicin (CAP),
- IV.OAB + lidocaine (LDK),
Cystometry was performed under urethane anaesthesia (1 h after catheter implantation, infusion rate – 0.046 ml/min.), after 24 h of the 4thCYP dose in group II, after 24 h of the 4thCYP and CAP in group III, after 24 h of the 4thCYP within 30 min. after LDK in group IV, after 24 h of the CAP in group V, after 30 min. of the LDK in group VI. 1mM CAP or 2% LDK were instilled at a rate of 0.15 ml/min. and left contact with the mucosa for 15 and 30 minutes, respectively. The measurements in each animal represent the average of 5 bladder micturition cycles, after obtaining repetitive voiding. We recorded: BP (basal pressure), PT (threshold pressure), MVP (micturition voiding pressure), ICI (intercontraction interval), Compliance, fBC (functional bladder capacity), MI (motility index), DI (detrusor index) and DOI (detrusor overactivity index).
CYP leads to decrease of MVP, ICI, fBC and compliance. Also increase of BP, DI, MI were observed. CAP produced complete inhibition of detrusor contractility. We observed a phasic detrusor contractions of low amplitude with accompanying increased intravesical pressure. As a consequence of the lack of periodically generated MVP and incomplete bladder empting, constantly lasting urine retention occured. In case of critical bladder fulfil achievement we recorded constant, dripping flow of urine through the urethra. Contrary, LDK leads to increase of ICI, compliance, fBC and DI. CAP and LDK reduced the severity of OAB, leading to the improvement of cystometric parameters. Compared to rats with chronic OAB we observed, increase of ICI, fBC, compliance. Also decrease of DOI and MI were observed. Surprisingly, MVP was higher after LDK, compared to control animals with chronic OAB.
CYP-induced cystitis leads to the OAB in rats. The modulation of C-fibres activity by CAP and LDK reduces the severity of detrusor overactivity in rats with chronic OAB, and improve its urodynamic estimation. This observations confirm the hypothesis, that in pathophysiology of overactive bladder the pivotal role play two types of unmyelinated bladder afferent C-fibres, both capsaicin-sensitive and capsaicin-resistant.
© 2009 European Association of Urology. Published by Elsevier Inc. All rights reserved.