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Open Access Highly Accessed Research article

Neuromodulation attenuates bladder hyperactivity in a rat cystitis model

Xin Su1*, Angela Nickles2 and Dwight E Nelson1

Author Affiliations

1 Medtronic, Inc, Neuromodulation Research, 7000 Central Avenue, Minneapolis, MN 55432, USA

2 Medtronic, Inc, Physiology Research Laboratory, 11520 Yellow Pine St, Coon Rapids, MN 55448, USA

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BMC Urology 2013, 13:70  doi:10.1186/1471-2490-13-70

Published: 6 December 2013

Abstract

Background

We investigated the regulation of urinary bladder function by electrical stimulation of the L6 spinal nerve (SN) using cystometry in normal rats and in rats with cystitis induced by intravesical infusion of dilute acetic acid.

Methods

In anesthetized rats, a cannula was placed into the bladder dome for saline/acetic acid infusion and intravesical pressure monitoring. Threshold pressure (TP), basal pressure (BP) and inter-contraction interval (ICI) were measured from the bladder pressure recording and void volume (VV) was measured by weighing the voided fluid.

Results

Comparison of cystometrograms obtained with infusion of saline or acetic acid showed that acetic acid decreases TP, ICI and VV. These excitatory effects, characteristic of acetic acid induced bladder hyperactivity, were significantly reversed by bilateral SN stimulation (P <0.05, vs pre-stimulation, Student t-test). In saline perfused rats, one hour of bilateral SN stimulation at 10 Hz and at motor threshold (0.19 ± 0.01 milliamps) increased ICI (265%) and VV (217%). In rats perfused with acetic acid, the corresponding increases produced by SN stimulation were 350% for ICI and 383% for VV. The percentage increases in the acetic acid-treated group were not significantly higher than those in saline-treated group.

Conclusions

Using continuous flow cystyometry, we find that SN stimulation can produce effects on micturition consistent with its effects on isovolumetric model, and consistent with the therapeutic effect observed with InterStim® therapy in overactive bladder patients. Although the effect of SN stimulation was slightly greater in bladder irritated over normal rats, the difference was not statistically significant.

Keywords:
Electrical stimulation; Spinal nerve; Bladder; Micturition; Acetic acid; Neuromodulation