Sex difference in the contribution of GABAB receptors to tibial neuromodulation of bladder overactivity in cats

Abstract

This study investigated the role of γ-aminobutyric acid subtype B (GABA_B) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical administration of dilute (0.5%) acetic acid (AA) in α-chloralose-anesthetized cats. To inhibit bladder overactivity, tibial or pudendal nerve stimulation (TNS or PNS) was applied at 5 Hz and two or four times threshold (T) intensity for inducing toe or anal sphincter twitch. TNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 173.8 ± 16.2 or 198.5 ± 24.1%, respectively, of control capacity. Meanwhile, PNS at 2T or 4T intensity significantly (P < 0.05) increased the bladder capacity to 217 ± 18.8 and 221.3 ± 22.3% of control capacity, respectively. CGP52432 (a GABA_B receptor antagonist) at intravenous dosages of 0.1-1 mg/kg completely removed the TNS inhibition in female cats but had no effect in male cats. CGP52432 administered intravenously also had no effect on control bladder capacity or the pudendal inhibition of bladder overactivity. These results reveal a sex difference in the role of GABA_B receptors in tibial neuromodulation of bladder overactivity in cats and that GABA_B receptors are not involved in either pudendal neuromodulation or irritation-induced bladder overactivity.

Keywords: GABA; bladder; cat; neuromodulation.

Fig. 2.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by tibial nerve stimulation (TNS) in female cats. A: repeated CMGs at different cumulative doses of CGP52432 were performed during acetic acid (AA) infusion with or without TNS. Black bars under the pressure trace indicate TNS duration. TNS: 5 Hz, 0.2 ms, T = 3 V. Infusion rate = 2 ml/min. B: normalized bladder capacity measured under different conditions (n = 5 cats). *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA). #Significantly (P < 0.05, Bonferroni comparisons) different from the bladder capacity measured during TNS before CGP52432 treatment (one-way ANOVA).

Fig. 4.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by tibial nerve stimulation (TNS) in cats of different genders (n = 5 female + 5 male). Normalized bladder capacity measured under different conditions. *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA).

Fig. 6.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by pudendal nerve stimulation (PNS) in female cats. A: repeated CMGs at different cumulative doses of CGP52432 were performed during acetic acid (AA) infusion with or without PNS. Black bars under the pressure trace indicate PNS duration. PNS: 5 Hz, 0.2 ms, T = 0.42 V. Infusion rate = 2 ml/min. B: normalized bladder capacity measured under different conditions (n = 5 cats). *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA).

Fig. 8.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by pudendal nerve stimulation (PNS) in cats of different genders (n = 5 female + 5 male). Normalized bladder capacity measured under different conditions. *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA).

Fig. 1.

Tibial nerve stimulation (TNS) inhibited the bladder overactivity induced by acetic acid (AA) irritation. A: representative cystometrogram (CMG) tracings with/without TNS during AA infusion into the bladder. Black bars under the pressure trace indicate TNS duration. TNS: 5 Hz, 0.2 ms, T = 3 V. Infusion rate = 2 ml/min. B: normalized bladder capacities measured during CMGs with/without TNS (n = 10 cats). The capacity was normalized to the AA control CMG. *Significantly (P < 0.05, Bonferroni comparisons) different from the control (one-way ANOVA). C: nonnnormalized bladder capacities for every animal.

Fig. 5.

Pudendal nerve stimulation (PNS) inhibited the bladder overactivity induced by acetic acid (AA) irritation. A: representative CMG tracings with/without PNS during AA infusion into the bladder. Black bars under the pressure trace indicate PNS duration. PNS: 5 Hz, 0.2 ms, T = 0.75 V. Infusion rate = 2 ml/min. B: normalized bladder capacities measured during CMGs with/without PNS (n = 10 cats). The capacity was normalized to the AA control CMG. *Significantly (P < 0.05, Bonferroni comparisons) different from the control (one-way ANOVA). C: nonnormalized bladder capacities for every animal.

Fig. 3.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by tibial nerve stimulation (TNS) in male cats. A: repeated CMGs at different cumulative doses of CGP52432 were performed during acetic acid (AA) infusion with or without TNS. Black bars under the pressure trace indicate TNS duration. TNS: 5 Hz, 0.2 ms, T = 0.6 V. Infusion rate = 1 ml/min. B: normalized bladder capacity measured under different conditions (n = 5 cats). *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA).

Fig. 7.

Effect of CGP52432 (intravenous) on the inhibition of bladder overactivity induced by pudendal nerve stimulation (PNS) in male cats. A: repeated CMGs at different cumulative doses of CGP52432 were performed during acetic acid (AA) infusion with or without PNS. Black bars under the pressure trace indicate PNS duration. PNS: 5 Hz, 0.2 ms, T = 1.5 V. Infusion rate = 2 ml/min. B: normalized bladder capacity measured under different conditions (n = 5 cats). *Significantly (P < 0.05, Bonferroni comparisons) different from control at different dosages of CGP52432 (two-way ANOVA).