Cystitis‐induced bladder overactivity is prevented by inhibition of N‐methyl‐d‐aspartate receptor‐mediated inflammatory responses in the urinary bladder (1131.5)

We previously show that NMDAR‐mediated signaling pathways play a significant role in regulating spinal plasticity during cyclophosphamide (CYP) ‐induced cystitis. Here we show that administration of a specific NMDAR antagonist MK801 (3mg/kg body weight, i.v.) to cystitis rats reversed bladder overactivity and inflammation at 48 h post drug treatment. In metabolic tests, MK801‐treated cystitis group had an average of 3.3 ± 1.0 voiding per hour whereas the group treated with CYP alone showed an average of 15.1 ± 5.8 voiding per hour (n=5, p<0.05). Cystometry results show that MK801 treatment of cystitis animals had a significant longer intermicturition intervals (192.0 ± 15.9 seconds(s)) when compared to CYP treatment alone (48.8 ± 4.6s, n=3, p<0.05). MK801 treatment also decreased cystitis‐induced increases in the ratio of bladder weight to body weight (CYP: 0.73 ± 0.09 mg/g; CYP+MK801: 0.35 ± 0.02 mg/g; n=5, p<0.05), and restored the integrity of urothelium damaged by CYP treatment. The effects of MK801 on cystitis‐induced bladder inflammation was also examined by its ability in reversing the elevated expression levels of pro‐inflammatory factors interlukin (IL)‐1alpha, IL‐6 and TNFalpha in the urinary bladder during cystitis. Taken together, we show that blockade of NMDAR‐mediated pathways can be an effective regimen in treatment of cystitis‐associated bladder overactivity and inflammation. Grant Funding Source : NIH DK077917