Effects of Saphenous Nerve Stimulation in an Irritation Induced Hyperactive Bladder Model – A Study in Anesthetized Rats

Moazzam, Zainab1; Yoo, Paul B.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 showed that stimulation of the SAFN can significantly affect the bladder contraction rate (BCR) and bladder capacity in healthy anesthetized rats. Therefore, in this study, we aimed to investigate the inhibitory efficacy of SAFN in an artificial hyperactive model where the bladder was chemically irritated via acetic acid (AA). Results from this study provide a deeper insight into the possible mechanisms involved in SAFN-mediated bladder inhibition.

Methods: A continuous urodynamic model was used in 7 urethane-anesthetized rats. The bladder was catheterized at the dome and connected in series with a pressure transducer and an infusion pump to constantly infuse saline and/or 0.1% AA. Data was collected following an hour of constant saline infusion to allow for bladder stabilization. A bipolar nerve cuff electrode was placed on the SAFN trunk to provide electrical stimulations. Stimulation trials were conducted for 40 minutes at 25 μA while the frequency was altered between 10 Hz and 20 Hz. The following parameters were evaluated: baseline pressure (BP); contraction amplitude (CA) and inter-contraction interval (ICI). All values were expressed as normalized values from saline baseline while all statistical comparisons were made with the AA pre-stimulation phase.

Results: An average irritation period of 87.7±15.6 minutes (range: 44 minutes – 150 minutes) was provided using continuous infusion of 0.1% AA following which, there was a notable decrease in the ICI (average: 30.8±16.0 %), an increase in the BP(average: 11.5±7.3%) and a reduction in the CA (average: 21.9±8.3%). Compared to the AA pre-stimulation phase, no significant changes in bladder parameters were observed during and/or post- SAFN stimulation. In 3 out of 7 trials conducted at 10 Hz and 20 Hz, prolonged ICI intervals were observed following SAFN stimulation however, no episodes of systemic loss of bladder activity were reported.

Conclusions: Present findings suggest a lack of bladder-modulatory effect by SAFN in an acute irritation-induced model. One reason for this could be the patho-physiological pathways activated by AA to induce hypersensitization of the nociceptive afferent fibers. We hypothesize that an increase in activity within these neural pathways might present a masking/blocking effect for SAFN-mediated reflexes either at a spinal or at a supra-spinal level. Studies are currently on-going to further explore the central pathways associated with this reflex.