Prolonged Suppression of Bladder Function via Saphenous Nerve Stimulation: A Study in Anesthetized Rats

Moazzam, Zainab 1 ; Yoo, Paul 1, 2

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Department of Electrical and Computer Engineering, University of Toronto

Background: Overactive bladder (OAB) is a chronic medical condition that is typically characterized by symptoms of urgency, incontinence and nocturia. The debilitating effects of this disorder affects nearly one in every six Canadians over the age of 35 years. Peripheral nerve stimulation is a minimally invasive yet effective treatment for OAB but, the mechanism of action remains unknown. Previously, we developed a computational model that suggested saphenous nerve (SAFN) as a major neural target that is co-activated during percutaneous tibial nerve stimulation (PTNS) and our recent pre-clinical work has also shown that stimulation of the SAFN can significantly reduce the bladder contraction rate (BCR) in a continuous urodynamic model. Therefore, in our lab, we are optimizing the bladder-inhibitory output achieved by saphenous nerve (SAFN) stimulation. The goals of the present study were to: (1) characterize the influence of SAFN stimulation on urodynamic parameters other than the BCR and (2) investigate the effect of stimulus duration on SAFN-mediated bladder-inhibitory reflexes.

Methods: A continuous urodynamic model was used in 9 urethane-anesthetized rats. The bladder was catheterized at the dome and connected in series with a pressure transducer and an infusion pump. A bipolar nerve cuff electrode was placed on the SAFN trunk to provide electrical stimulations. Finite duration trials (10, 20 and 40 minutes) of electrical pulses were applied at 25 µA and the stimulation frequency was varied between 10 Hz and 20 Hz. The following parameters were evaluated: baseline pressure (BP); contraction amplitude (CA) and peak pressure (PP). All values were expressed as a percent change from baseline.

Results: The duration of nerve stimulation had markedly different effects on bladder activity in response to 10 Hz SAFN stimulation. Compared to 10 minutes of stimulation, the BP significantly increased during 40 minutes of stimulation (14.4±7.5%; p=0.0016) and remained elevated 30 min post-stimulation (26±10.4%). Similarly, the CA significantly decreased to 31.6±9.1% (p<0.001) with 40 minutes of SAFN stimulation and subsided to 53.3±19.3% within 30-minutes post-stimulation. No significant differences were observed in the PP with stimulus duration. In 3 of the 6 trials conducted at 40 minutes, shifts in BP and CA resulted in complete inhibition of bladder contractions that lasted on average for 55-minutes post-stimulation. Conversely, no significant differences were observed with stimulus duration in CA or PP during 20 Hz SAFN stimulation.

Conclusions: In addition to the stimulation amplitude and frequency, we found that the duration of electrical stimulation at 10 Hz can also have a significant impact on the the urodynamic parameters that can significantly influence the overall bladder-inhibitory response in anesthetized rats. Clinical studies are needed to determine whether SAFN stimulation can elicit therapeutic effects in OAB patients.