Sacral neuromodulation blocks pudendal inhibition of reflex bladder activity in cats: insight into the efficacy of sacral neuromodulation in Fowler's syndrome

Abstract

This study tested the hypothesis that sacral neuromodulation, i.e., electrical stimulation of afferent axons in sacral spinal root, can block pudendal afferent inhibition of the micturition reflex. In α-chloralose-anesthetized cats, pudendal nerve stimulation (PNS) at 3-5 Hz was used to inhibit bladder reflex activity while the sacral S1 or S2 dorsal root was stimulated at 15-30 Hz to mimic sacral neuromodulation and to block the bladder inhibition induced by PNS. The intensity threshold (T) for PNS or S1/S2 dorsal root stimulation (DRS) to induce muscle twitch of anal sphincter or toe was determined. PNS at 1.5-2T intensity inhibited the micturition reflex by significantly ( P < 0.01) increasing bladder capacity to 150-170% of control capacity. S1 DRS alone at 1-1.5T intensity did not inhibit bladder activity but completely blocked PNS inhibition and restored bladder capacity to control level. At higher intensity (1.5-2T), S1 DRS alone inhibited the micturition reflex and significantly increased bladder capacity to 135.8 ± 6.6% of control capacity. However, the same higher intensity S1 DRS applied simultaneously with PNS, suppressed PNS inhibition and significantly ( P < 0.01) reduced bladder capacity to 126.8 ± 9.7% of control capacity. S2 DRS at both low (1T) and high (1.5-2T) intensity failed to significantly reduce PNS inhibition. PNS and S1 DRS did not change the amplitude and duration of micturition reflex contractions, but S2 DRS at 1.5-2T intensity doubled the duration of the contractions and increased bladder capacity. These results are important for understanding the mechanisms underlying sacral neuromodulation of nonobstructive urinary retention in Fowler's syndrome.

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

Fig. 1.

Electrical stimulation (1–1.5T) of the S1 dorsal root did not increase bladder capacity but removed the increase in bladder capacity induced by pudendal nerve stimulation (PNS). A: repeated cystometrogram (CMG) traces with/without PNS and/or S1 dorsal root stimulation (DRS). The black bars under the CMG traces indicate the duration of PNS and/or S1 DRS. PNS: 5 Hz, 0.2 ms, 1.5T = 0.36 V. S1 DRS: 30 Hz, 0.2 ms, 1.5T = 0.3 V. T: threshold intensity for inducing anal twitch; infusion rate: 2 ml/min. B: summarized bladder capacities measured during different CMGs (n = 7 cats). *Significant difference (P < 0.01, one-way ANOVA). PNS: 3 or 5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.6 V. S1 DRS: 15 or 30 Hz, 0.2 ms, 1–1.5T, T = 0.16–0.6 V.

Fig. 2.

Effects of pudendal nerve stimulation (PNS) and/or S1 dorsal root stimulation (DRS) on the amplitude (A), duration (B), and area under curve (C) of micturition reflex contraction (n = 7 cats). PNS: 3 or 5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.6 V. S1 DRS: 15 or 30 Hz, 0.2 ms, 1–1.5T, T = 0.16–0.6 V.

Fig. 3.

Electrical stimulation (1.5–2T) of the S1 dorsal root increased bladder capacity, but also removed the increase in bladder capacity induced by pudendal nerve stimulation (PNS). A: repeated cystometrogram (CMG) traces with/without PNS and/or S1 dorsal root stimulation (DRS). The black bars under the CMG traces indicate the durations of PNS and/or S1 DRS. PNS: 5 Hz, 0.2 ms, 1.5T = 0.9 V. S1 DRS: 15 Hz, 0.2 ms, 2T = 0.4 V. T: threshold intensity for inducing anal twitch; infusion rate: 3 ml/min. B: summarized bladder capacities measured during different CMGs (n = 6 cats). *Significant difference (P < 0.05, one-way ANOVA). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.6 V. S1 DRS: 15 or 30 Hz, 0.2 ms, 1.5–2T, T = 0.16–0.36 V.

Fig. 4.

Effects of pudendal nerve stimulation (PNS) and/or S1 dorsal root stimulation (DRS) on the amplitude (A), duration (B), and area under curve (C) of micturition reflex contractions (n = 6 cats). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.6 V. S1 DRS: 15 or 30 Hz, 0.2 ms, 1.5–2T, T = 0.16–0.36 V.

Fig. 5.

Electrical stimulation (1T) of S2 dorsal root did not increase bladder capacity but slightly reduced the increase in bladder capacity induced by pudendal nerve stimulation (PNS). A: repeated cystometrogram (CMG) traces with/without PNS and/or S2 dorsal root stimulation (DRS). The black bars under the CMG traces indicate the durations of PNS and/or S2 DRS. PNS: 5 Hz, 0.2 ms, 1.5T = 0.36 V. S2 DRS: 30 Hz, 0.2 ms, 1T = 0.3 V. T: threshold intensity for inducing anal twitch; infusion rate: 2 ml/min. B: summarized bladder capacities measured during different CMGs (n = 5 cats). *Significant difference (P < 0.01, one-way ANOVA). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.56 V. S2 DRS: 30 Hz, 0.2 ms, 1T, T = 0.14–0.3 V.

Fig. 6.

Effects of pudendal nerve stimulation (PNS) and/or S2 dorsal root stimulation (DRS) on the amplitude (A), duration (B), and area under curve (C) of micturition reflex contractions (n = 5 cats). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.56 V. S2 DRS: 30 Hz, 0.2 ms, 1T, T = 0.14–0.3 V.

Fig. 7.

Electrical stimulation (1.5–2T) of S2 dorsal root increased bladder capacity but did not reduce the increase in bladder capacity induced by pudendal nerve stimulation (PNS). A: repeated cystometrogram (CMG) traces with/without PNS and/or S2 dorsal root stimulation (DRS). The black bars under the CMG traces indicate the durations of PNS and/or S1 DRS. PNS: 5 Hz, 0.2 ms, 2T = 0.48 V. S2 DRS: 30 Hz, 0.2 ms, 2T = 0.28 V. T: threshold intensity for inducing anal twitch; infusion rate: 1 ml/min. B: summarized bladder capacities measured during different CMGs (n = 5 cats). *Significant difference (P < 0.01, one-way ANOVA). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.56 V. S2 DRS: 30 Hz, 0.2 ms, 1.5–2T, T = 0.14–0.3 V.

Fig. 8.

Effects of pudendal nerve stimulation (PNS) and/or S2 dorsal root stimulation (DRS) on the amplitude (A), duration (B), and area under curve (C) of micturition reflex contractions (n = 5 cats). PNS: 3–5 Hz, 0.2 ms, 1.5–2T, T = 0.2–0.56 V. S2 DRS: 30 Hz, 0.2 ms, 1.5–2T, T = 0.14–0.3 V.

Fig. 9.

Hypothetical spinal mechanisms that underlie: first, the inhibition of the micturition reflex pathway by afferent axons in the pudendal nerve, and second, the suppression of the pudendal afferent inhibitory pathway by electrical stimulation of the sacral S1 dorsal root. Pudendal afferents activate an inhibitory interneuron (2) that suppresses activity of a spinal tract neuron (3) on the ascending limb of the micturition reflex. S1 dorsal root stimulation activates an inhibitory interneuron (1) that suppresses activity of the interneuron (2) in the pudendal afferent inhibitory pathway.