Editorial Comment from Dr Kitta to Effect of intrathecal administration of E‐series prostaglandin 1 receptor antagonist in a cyclophosphamide‐induced cystitis rat model

Abstract

At present, anticholinergic agents are the mainstay of pharmacological treatment of overactive bladder (OAB), and the definitive pharmacological treatment for interstitial cystitis/ painful bladder syndrome (IC/PBS) is limited. The cause of these situations is the poor understanding of disease pathophysiology and insufficient drugs of central action for lower urinary tract dysfunction. This paper throws a new light on the treatment for the pathological condition of lower urinary tract dysfunction. The authors described a study evaluating the possibility that blockade of the spinal E-series prostaglandin 1 (EP1) receptor by ONO-8711 might have a therapeutic potential in the control of urinary frequency. As previous studies reported, systemic administration of EP1 receptor antagonist improved bladder function in some pathological rat models. However, we did not know the effective site of EP1 receptor antagonist. From their result, the authors speculated that EP1 receptor antagonist blocks the afferent signal of spinal prostaglandin E2 (PGE2) through the EP1 receptor. This is a really interesting new concept. In the present study, intracerebral administration of EP1 receptor antagonist was not tested. Therefore, we could not speculate whether the improvement of bladder function after systemic administration of EP1 receptor antagonist was caused partly by suppression of the EP1 receptor in the supraspinal site. Indeed, the tissue PGE2 level at the ventral horn of cyclophosphamide (CYP)-induced cystitis rats was not significantly different from control rats. These data suggest that EP1 antagonist injected intrathecally mainly inhibits the afferent effect of PGE2 through the EP1 receptor. However, the CYP-induced cystitis model was one of the bladder nociceptive cystitis models. We do not really know whether the other bladder dysfunction models, such as the bladder outlet obstruction model or IC/PBS models, have the same expression of the EP1 receptor in the spinal cord. Furthermore, many researchers reported that the EP1 receptor is abundant in the brain. These points should be solved in the future. Time and effort have been invested in the characterization of the central mechanisms controlling the micturition reflexes, and now we move on to find novel drugs for micturition disorders with a central effect.