Sacral neuromodulation of bladder underactivity induced by prolonged pudendal afferent firing in cats

Abstract

This study examined the effect of sacral neuromodulation on persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PudNS). In 10 α-chloralose-anesthetized cats, repetitive application of 30-min PudNS induced bladder underactivity evident as an increase in bladder capacity during a cystometrogram (CMG). S1 or S2 dorsal root stimulation (15 or 30 Hz) at 1 or 1.5 times threshold intensity (T) for inducing reflex hindlimb movement (S1) or anal sphincter twitch (S2) was applied during a CMG to determine if the stimulation can reverse the bladder underactivity. Persistent (>3 h) bladder underactivity consisting of a significant increase in bladder capacity to 163.1 ± 11.3% of control was induced after repetitive (1-10 times) application of 30-min PudNS. S2 but not S1 dorsal root stimulation at 15 Hz and 1 T intensity reversed the PudNS-induced bladder underactivity by significantly reducing the large bladder capacity to 124.3 ± 12.9% of control. Other stimulation parameters were not effective. After the induction of persistent underactivity, recordings of reflex bladder activity under isovolumetric conditions revealed that S2 dorsal root stimulation consistently induced the largest bladder contraction at 15 Hz and 1 T when compared with other frequencies (5-40 Hz) or intensities (0.25-1.5 T). This study provides basic science evidence consistent with the hypothesis that abnormal pudendal afferent activity contributes to the bladder underactivity in Fowler's syndrome and that sacral neuromodulation treats this disorder by reversing the bladder inhibition induced by pudendal nerve afferent activity.

Keywords: bladder; neuromodulation; pudendal; sacral; underactivity.

Figure 1.

Prolonged increase in bladder capacity by repeated (5 times) application of 30-min pudendal nerve stimulation (PudNS). The 30-min PudNS (5 Hz, 0.2 ms) was applied at intensity 3 T for 3 times followed by additional 2 times at 6-T intensity. After repeated PudNS, the increased bladder capacity was maintained in the following 7 CMGs (top-down in sequence) performed in a 1.5-h period. S1 dorsal root stimulation (15 or 30 Hz, 0.2 ms) at 1 or 1.5 T applied during the CMGs did not reverse the increased bladder capacity. The dashed line indicates the control bladder capacity. T = 1.2 V for PudNS, but T = 0.1 V for S1 dorsal root stimulation. Bladder infusion rate = 2 mL/min. The CMGs in this figure were obtained from the same animal. CMGs, cystometrograms; T, threshold intensity for inducing anal twitch.

Figure 2.

S2 dorsal root stimulation (15 Hz, 1 T) reversed the increase in bladder capacity induced by repeated PudNS. The recordings in this figure were obtained from the same cat as shown in Fig. 1. The 7 CMGs (top-down in sequence) were performed in a 1.5-h period following the CMGs in Fig. 1., i.e., the first CMG is the last CMG shown in Fig. 1. The dashed line indicates the same control bladder capacity as Fig. 1. T = 0.1 V. Bladder infusion rate = 2 mL/min. CMGs, cystometrograms.

Figure 3.

S2 dorsal root stimulation (15 Hz, 1 T) reversed the increase in bladder capacity induced by 30-min pudendal nerve stimulation (PudNS) but completely inhibited micturition contraction at a higher frequency (30 Hz) or intensity (1.5 T). The 30-min PudNS (5 Hz, 0.2 ms) was applied at 3 T intensity. After the PudNS, 13 CMGs were performed in a 3-h period, first in the left column and then in the right column. In the same column, the CMGs were performed in sequence from the top to the bottom. The last CMG in the left column is same as the first CMG in the right column. S1 dorsal root stimulation (right column) applied during the CMGs did not reverse the increased bladder capacity. The dashed lines indicate the control bladder capacity. T = 0.6 V for PudNS, T = 0.3 V for S1 dorsal root stimulation, and T = 0.6 V for S2 dorsal root stimulation. Bladder infusion rate = 2 mL/min. CMGs, cystometrograms; T, threshold intensity for inducing anal twitch.

Figure 4.

S2 dorsal root stimulation (15 Hz, 1 T) reversed the increase in bladder capacity induced by repeated 30-min pudendal nerve stimulation (PudNS). PudNS: 5 Hz, 0.2 ms, 3–6 T, 30 min, applied for 1–10 times. S1 dorsal root stimulation: 15 or 30 Hz, 0.2 ms, 1 or 1.5 T. S2 dorsal root stimulation: 15 or 30 Hz, 0.2 ms, 1 or 1.5 T. The 15 and 30 Hz were applied randomly in each test group (A, B, C, or D) but plotted in order. *Significantly (P < 0.05) different from the initial control (Dunnett’s multiple comparison). #Significantly (P < 0.05) different from the post-PudNS control (Dunnett’s multiple comparison). N = 10 cats.

Figure 5.

Bladder contractions induced by S2 dorsal root stimulation at different intensities (A) and frequencies (B). A: under isovolumetric conditions with the bladder volume significantly increased by prolonged pudendal nerve stimulation, S2 dorsal root stimulation (15 Hz) at intensity 1 T induced the largest (50–100 cmH₂O) bladder contractions in all 3 cats tested. B: under isovolumetric conditions, S2 dorsal root stimulation at 15 Hz induced the largest bladder contraction in every cat. Threshold (T) intensity for inducing anal twitch was used in cats 2 (0.06 V) and 3 (0.4 V), but 0.5 T was used in cat 1 (0.3 V). Note: the 15 Hz was tested at the beginning and the end to control the testing conditions. n = 3 cats for the summarized figures.