MP8-19 A NEW MECHANISM OF INFECTION-INDUCED BLADDER HYPERACTIVITY: LIPOPOLYSACCHARIDE CAUSES RAPID ATP RELEASE FROM UROTHELIUM AND STIMULATES THE MECHANOSENSORY AFFERENT PATHWAY

Abstract

understanding the mechanism of action of tibial neuromodulation therapy for overactive bladder. METHODS: 16 cats under isoflurane anesthesia underwent decerebration by surgical transection rostral to the superior colliculi. Then, multiple saline cystometrograms (CMGs) were performed under a-chloralose anesthesia to elicit micturition reflex contractions (>30 cmH2O). 30 minutes of continuous TNS at three times threshold intensity for inducing toe movement was then applied during isovolumetric bladder contractions at frequencies of either 5Hz or 30Hz. After each stimulation, five consecutive CMGs were performed to assess post-stimulation changes of bladder capacity. CMGs were then performed during TNS at either 5Hz or 30Hz. Next, the same stimulation protocol was repeated during AA irritation. At the end of each experiment, naloxone (an opioid receptor antagonist) was administered either intravenously (1 mg/kg) or directly into the brainstem (2.0-4.0 mg in 0.10.2 cc) followed by a series of CMGs with/without TNS. ANOVA tests were used to determine statistical significance (p<0.05). RESULTS: During saline infusion, 30 minutes of TNS significantly increased post-stimulation bladder capacity above controls with a mean increase of 27.2% (p<0.01) at a frequency of 5 Hz and 44.2% (p<0.01) at a frequency of 30 Hz. However, post-stimulation TNS inhibition was not observed during AA infusion. TNS applied during CMG significantly increased bladder capacity by 27.3% (saline, p<0.01) and 87.6% (AA, p<0.01) respectively over controls at 5 Hz, but failed to achieve significant inhibition at 30 Hz. Naloxone treatments significantly reduced control bladder capacity whether given intravenously (68.1% reduction, p<0.01) or directly into brainstem (58.8% reduction, p<0.01) and completely eliminated the acute TNS inhibition. CONCLUSIONS: Our results suggest: (1) the brainstem plays an important role in TNS inhibition of both non-nociceptive (saline distention) and nociceptive (AA irritation) bladder reflexes while the cerebrum is not necessary; (2) opioid receptors in the brainstem are involved in TNS inhibition of the nociceptive bladder reflex.