MP12-19 SPONTANEOUS MICTURITION BEHAVIOR AND CYSTOMETRIC EVALUATION OF BLADDER FUNCTION IN P2X7 RECEPTOR DEFICIENT MICE

METHODS: Female Sprague-Dawley rats (6 months age, n1⁄410) with SCI produced by complete transection of the Th2-3 spinal cord were used. Seven weeks after spinalization, liposomes only or liposomes conjugated with NGF antisense were administered intravesically. At 1 week after intravesical treatment, changes in blood pressure and heart rates during graded increases in intravesical pressure (20 to 60 cmH2O) were measured under urethane anesthesia. RESULTS: Themean arterial blood pressures was elevated and the mean heart rate was decreased during bladder distension with increasing distension pressures in a graded manner to 20, 40 and 60 cmH2O in the liposomeonly-treated group. The liposome-NGFantisense treatment suppressed the increases of mean blood pressures (2.3 e 0.8 mmHg; 83%decrease at 20 cmH2O, 11.3e 2.5mmHg; 64%decrease at 40 cmH2O, 14.7 e 1.7 mmHg; 62% decrease at 60 cmH2O) and the decreases of mean heart rates (-10 e 10 bpm; 66% increase at 20 cmH2O, -20 e 10 bpm; 50% increase at 40 cmH2O, -20 e 20 bpm; 75% increase at 60 cmH2O) compared to the liposome only-treated group. CONCLUSIONS: These results indicate that liposome-based local suppression of NGF in the bladder improved viscero-vascular reflexes after SCI. Since the expression of NGF in the bladder is increased after SCI based on previous studies, intravesical application of liposome NGF antisense conjugates may be an effective therapy for AD induced by bladder distension.