Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats

Abstract

Objective: To determine the role of opioid, β-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity.

Material and methods: In α-chloralose anesthetized cats, intravesical infusion of 0.5% acetic acid (AA) irritated the bladder and induced bladder overactivity. Electric stimulation (5 Hz, 0.2 ms, 0.16-0.7V) of S1 or S2 sacral dorsal roots inhibited the bladder overactivity. Naloxone, propranolol, or MTEP were given intravenously (i.v.) to determine different neurotransmitter mechanisms.

Results: AA significantly (p < 0.05) reduced bladder capacity to 7.7 ± 3.3 mL from 12.0 ± 5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p < 0.05) increased bladder capacity to 179.4 ± 20.0% or 219.1 ± 23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p < 0.001) reduced the control capacity to 38.3 ± 7.3% and the bladder capacity measured during S1 stimulation to 106.2 ± 20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p < 0.01) reduced bladder capacity from 251.8 ± 32.2% to 210.9 ± 33.3% during S2 stimulation, but had no effect during S1 stimulation. A similar propranolol effect also was observed in naloxone-pretreated cats. In propranolol-pretreated cats during S1 or S2 stimulation, MTEP (3 mg/kg) significantly (p < 0.05) reduced bladder capacity and naloxone (1 mg/kg) following MTEP treatment further reduced bladder capacity. However, a significant inhibition could still be induced by S1 or S2 stimulation after all three drugs were administered.

Conclusions: Neurotransmitter mechanisms in addition to those activating opioid, β-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.

Keywords: Bladder; cat; neuromodulation; neurotransmitter.

Figure 1

Effect of naloxone on inhibition of bladder overactivtiy induced by S1 or S2 dorsal root stimulation at motor threshold (T) intensity. a. Typical CMG traces from a cat. The black bar under the pressure trace indicates the stimulation duration. Stimulation: 5 Hz, 0.2 ms, T = 0.3V for S1, T = 0.16V for S2. Infusion rate = 2 mL/min. b. Normalized bladder capacity measured during repeated CMGs before and after naloxone treatment (N = 11 cats). * indicates a significant (p <0.001, two-way ANOVA) difference before and after naloxone treatment. # or $ indicates significantly (p <0.05, one-way ANOVA) different from control in the same treatment group.

Figure 2

Effect of propranolol on inhibition of bladder overactivity induced by S1 or S2 dorsal root stimulation at motor threshold (T) intensity. a. Typical CMG traces from a cat. The black bar under the pressure trace indicates stimulation duration. Stimulation: 5 Hz, 0.2 ms, T = 0.24V for S1, T = 0.2V for S2. Infusion rate = 2 mL/min. b. Normalized bladder capacity measured during repeated CMGs before and after propranolol treatment (N = 13 cats). * indicates a significant (p <0.01, two-way ANOVA) difference before and after propranolol treatment. # or $ indicates significantly (p <0.01, one-way ANOVA) different from control in the same treatment group.

Figure 3

Effect of propranolol on inhibition of bladder overactivity induced by S1 or S2 dorsal root stimulation at motor threshold (T) intensity in naloxone-pretreated cats. a. Typical CMG traces from a cat. The black bar under the pressure trace indicates stimulation duration. Stimulation: 5 Hz, 0.2 ms, T = 0.3V for S1, T = 0.26V for S2. Infusion rate = 3 mL/min. b. Normalized bladder capacity measured during repeated CMGs before and after propranolol treatment in naloxone-pretreated cats (N = 11). * indicates a significant (p <0.001, two-way ANOVA) difference before and after propranolol treatment. # or $ indicates significantly (p <0.05, one-way ANOVA) different from control in the same treatment group.

Figure 4

Effect of MTEP on inhibition of bladder overactivtiy induced by S1 or S2 dorsal root stimulation at motor threshold (T) intensity in propranolol-pretreated cats. a. Typical CMG traces from a cat. The black bar under the pressure trace indicates stimulation duration. Stimulation: 5 Hz, 0.2 ms, T = 0.7V for S1, T = 0.5V for S2. Infusion rate = 1 mL/min. b. Normalized bladder capacity measured during repeated CMGs before and after MTEP treatment in propranolol-pretreated cats (N = 13). * indicates a significant (p <0.05, two-way ANOVA) difference before and after MTEP treatment. # or $ indicates significantly (p <0.01, one-way ANOVA) different from control in the same treatment group.

Figure 5

Effect of naloxone on inhibition of bladder overactivity induced by S1 or S2 dorsal root stimulation at motor threshold (T) intensity in propranolol and MTEP-pretreated cats. a. Typical CMG traces from a cat. The black bar under the pressure trace indicates stimulation duration. Stimulation: 5 Hz, 0.2 ms, T = 0.4V for S1, T = 0.3V for S2. Infusion rate = 3 mL/min. b. Normalized bladder capacity measured during repeated CMGs before and after naloxone treatment in propranolol and MTEP-pretreated cats (N = 12). * indicates a significant (p <0.001, two-way ANOVA) difference before and after naloxone treatment. # or $ indicates significantly (p <0.05, one-way ANOVA) different from control in the same treatment group.