Effect of intrathecal administration of E-series prostaglandin 1 receptor antagonist in a cyclophosphamide-induced cystitis rat model

Objectives: To investigate the effect of intrathecal administration of E‐series prostaglandin 1 antagonist in cyclophosphamide‐induced murine cystitis. Methods: Female Wistar rats were used for this experimental study. Intrathecal administration of E‐series prostaglandin 1 antagonist (ONO‐8711; 0.5, 5 and 50 µg) in sham controls and rats with cystitis induced by a single intraperitoneal injection of cyclophosphamide (300 mg/kg) was assessed by evaluating micturition pressure and intercontraction interval using a conscious‐filling cystometry at 48 h after cyclophosphamide or saline injection. In both groups, prostaglandin E2 concentrations and the expression of E‐series prostaglandin 1 receptor in the spinal cord were measured by enzyme‐linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Results: Rats with cyclophosphamide‐induced cystitis showed a shorter intercontraction interval compared with controls, where the cumulative intrathecal administration of ONO‐8711 did not significantly change micturition pressure or intercontraction interval compared with the baseline. In rats with cyclophosphamide‐induced cystitis, each dose of ONO‐8711 significantly increased the intercontraction interval compared with the baseline (46% increase at 50 µg intrathecally). Polymerase chain reaction revealed the expression of E‐series prostaglandin 1 receptor in the spinal cord of both sham and cyclophosphamide‐induced cystitis rats. In rats with cyclophosphamide‐induced cystitis, PGE2 concentration in the dorsal horn of the L5‐6 spinal cord was significantly higher than that in controls (3.55 ± 1.24 vs 0.99 ± 0.06 pg/mg tissue). Conclusions: In rats with cyclophosphamide‐induced cystitis, urinary frequency seems to be caused by prostaglandin E2 acting on E‐series prostaglandin 1 receptor at the level of the spinal cord. Blockade of the spinal E‐series prostaglandin 1 receptor by ONO‐8711 might have a therapeutic potential in the control of interstitial cystitis/bladder pain syndrome.