Prolonged poststimulation inhibition of bladder activity induced by tibial nerve stimulation in cats

Abstract

Inhibition of bladder activity by tibial nerve stimulation was investigated in α-chloralose-anesthetized cats with an intact spinal cord. Short-duration (3-5 min) tibial nerve stimulation at both low (5 Hz) and high (30 Hz) frequencies applied repeatedly during rhythmic isovolumetric bladder contractions was effective in inhibiting reflex bladder activity. Both frequencies of stimulation were also effective in inducing inhibition that persisted after the termination of the stimulation. The poststimulation inhibitory effect induced by the short-duration stimulation significantly increased bladder capacity to 181.6 ± 24.36% of the control capacity measured before applying the stimulation. Thirty-minute continuous stimulation induced prolonged poststimulation inhibition of bladder activity, which lasted for more than 2 h and significantly increased bladder capacity to 161.1 ± 2.9% of the control capacity. During the poststimulation periods, 5-Hz stimulation applied during the cystometrogram elicited a further increase (~30% on average) in bladder capacity, but 30-Hz stimulation was ineffective. These results in cats support the clinical observation that tibial nerve neuromodulation induces a long-lasting poststimulation inhibitory effect that is useful in treating overactive bladder symptoms.

Figures

Fig. 1.

Tibial nerve stimulation at both 5 Hz (A) and 30 Hz (B) and at different stimulus intensities inhibits rhythmic isovolumetric bladder contractions. The black bars under pressure traces indicate the stimulation duration. T, stimulation intensity threshold for inducing toe movement. Stimulation pulse width = 0.2 ms. T = 3.5 V. The white arrows indicate bladder pressure increases induced by transient manual pressure on the lower abdomen.

Fig. 2.

Bladder capacity was significantly increased by repeated tibial nerve stimulation applied during rhythmic isovolumetric contractions. A: cystometrogram (CMG) performed before repeated short-duration tibial nerve stimulation was applied during rhythmic isovolumetric contractions. B: selected bladder pressure traces during rhythmic isovolumetric contractions showing 3 sequential recordings spread over approximately a 90-min period showing inhibition of rhythmic bladder contractions by short-duration tibial nerve stimulation and spontaneous recovery from inhibition in the top recording. Bottom 2 recordings show failure of spontaneous recovery after more intense stimulation even with manual pressure but recovery after infusing additional fluid into the bladder. C: CMG after repeated short-duration tibial nerve stimulation shows increased bladder capacity. All records are from the same cat and the record in C was obtained 10 min after the last record in B. The black bars under pressure traces indicate the stimulation duration. Stimulation: frequency = 5 Hz; pulse width = 0.2 ms; T = 3 V. The white arrows indicate a bladder pressure increase induced by transient manual pressure on the lower abdomen. Infusion rate = 1 ml/min.

Fig. 3.

A: short-duration tibial nerve stimulation at intensities at or above 2 times T intensity for inducing toe movement significantly inhibited rhythmic isovolumetric bladder contractions. B: bladder capacity is also significantly increased after repeated tibial nerve stimulation applied during the rhythmic isovolumetric bladder contractions. Stimulation: pulse width = 0.2 ms; intensity 0.5–4 T (1.5–21 V). *Significant difference from 100% in A. *Significant difference between groups in B; n = 6.

Fig. 4.

Poststimulation inhibitory effect of tibial nerve stimulation is evident during repeated CMG testing. A: bladder capacity was not significantly changed during repeated CMGs in the absence of nerve stimulation. Note: after the initial and 5th CMG, the bladder was maintained for 30 min in a distended condition and exhibited rhythmic contractions. B: bladder capacity was significantly increased after a 30-min tibial nerve stimulation following the initial CMG, but was not further increased after the second 30-min tibial nerve stimulation. Five repeated CMGs (1st-5th and 6th-10th) were performed within 1.5–2 h after each 30-min period of stimulation. The vertical dashed line indicates the control bladder capacity. Infusion rate: 1 ml/min. The horizontal black bar indicates the 30-min tibial nerve stimulation. Stimulation: frequency 5 or 30 Hz; pulse width = 0.2 ms; intensity 9 V (3 T).

Fig. 5.

Prolonged poststimulation inhibition induced by 30-min tibial nerve stimulation. A: bladder capacity was significantly increased after the first 30-min tibial nerve stimulation, but was not further increased after the second 30-min stimulation. The poststimulation inhibitory effect lasted more than 1.5–2 h. B: increase of bladder capacity did not occur if the 30-min stimulation was preceded by repeated short-duration tibial nerve stimulation during rhythmic isovolumetric contractions. However, note that the repeated short-duration stimulation also increases bladder capacity as shown in Fig. 3B. Stimulation: pulse width = 0.2 ms; intensity 7.5–14 V (2–4 T). *Statistically significant difference between the control and treatment groups. Vertical dashed line indicates the time of the second 30-min stimulation. Control: n = 12. Stimulation: n = 9 in A, n = 5 in B.

Fig. 6.

A: after the second 30-min tibial nerve stimulation, 5-Hz tibial nerve stimulation applied during the CMG further increased bladder capacity during the 11th CMG, but subsequent 30-Hz stimulation during the 12th CMG did not increase the bladder capacity. Infusion rate: 1 ml/min. Stimulation: pulse width = 0.2 ms; T = 3 V. B: summarized results (n = 9). Stimulation: pulse width = 0.2 ms; intensity 2–4 T. *Statistically significant difference.