Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats.

Abstract

OBJECTIVE: To determine the role of opioid, &#x3b2;-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity. MATERIAL AND METHODS: In &#x3b1;-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&#x2009;<&#x2009;0.05) reduced bladder capacity to 7.7&#x2009;&#xb1;&#x2009;3.3 mL from 12.0&#x2009;&#xb1;&#x2009;5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p&#x2009;<&#x2009;0.05) increased bladder capacity to 179.4&#x2009;&#xb1;&#x2009;20.0% or 219.1&#x2009;&#xb1;&#x2009;23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p&#x2009;<&#x2009;0.001) reduced the control capacity to 38.3&#x2009;&#xb1;&#x2009;7.3% and the bladder capacity measured during S1 stimulation to 106.2&#x2009;&#xb1;&#x2009;20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p&#x2009;<&#x2009;0.01) reduced bladder capacity from 251.8&#x2009;&#xb1;&#x2009;32.2% to 210.9&#x2009;&#xb1;&#x2009;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&#x2009;<&#x2009;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, &#x3b2;-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.