Amplitude-dependent modulation of bladder function with tibial nerve stimulation in an anesthetized rat model

Paquette, Jason P  1  ;   Yoo, Paul B  1, 2  

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

Overactive bladder (OAB) is a syndrome characterized by symptoms of increased urgency and frequency that affects 8-9% of Canadian adults. Percutaneous Tibial Nerve Stimulation (PTNS) is a minimally-invasive OAB therapy in which the tibial nerve is electrically stimulated by a needle electrode inserted directly above the ankle. The efficacy of PTNS has been proven clinically; however, success rates are highly variable and the mechanism of action is not fully understood. Recent work in our lab showed that repeated trials of tibial nerve stimulation (TNS) can elicit significant decreases in the bladder contraction rate (BCR). However, the functional implications of modulating the BCR are not clear. In this study, we aimed to correlate changes in BCR with specific functional changes in bladder function, such as bladder capacity (BC) and voiding efficiency (VE). We hypothesized that changes in these parameters are dependent on the stimulation amplitude. In 6 urethane-anesthetized rats, a surgically-implanted bipolar nerve cuff electrode was used to apply trains of TNS that were set at four different amplitude settings: 0T (no stimulation), 6T (Aβ fiber activation), 15T (Aβ & Aδ fiber activation), and 100T (Aβ, Aδ, & C fiber activation). Here, T is defined as the foot motor threshold. The bladder was instrumented with a suprapubic catheter to provide continuous saline infusion, both ureters were transected and drained externally, and the voided fluids were collected and electronically measured in real-time. Following an initial two-hour period of saline infusion (baseline), four sets of stimulation trials (30 min pre-TNS + 30 min TNS + 30 min post-TNS = total 90 minutes) applied at different amplitudes (0T, 6T, 15T, and 100T) in a randomized order. Our preliminary data show that stimulation-evoked changes in the BC and VE occur in an amplitude-dependent manner and are observed primarily during the post-TNS period. Compared to the pre-TNS period, changes in the post-TNS BC increased with the stimulation amplitude (mean ± SEM): 106±7% (0T), 111±11% (6T), 137±12% (15T), and 156±8% (100T). Conversely, the post-TNS VE exhibited a decrease as the stimulation amplitude was increased: 101±9% (0T), 94±8% (6T), 90±14% (15T), and 55±17% (100T). The preliminary results of this study point towards increased post-stimulation effects of treatment at stimulation amplitudes likely to activate small diameter afferent nerve fibers within the tibial nerve.