Editorial comment on: Intravesical botulinum toxin A administration inhibits COX-2 and EP4 expression and suppresses bladder hyperactivity in cyclophosphamide-induced cystitis in rats.

Interstitial cystitis (IC)—or painful bladder syndrome (BPS)—is a chronic bladder condition characterised by “the complaint of suprapubic pain related to bladder filling, accompanied by increased daytime and night-time frequency” [1]. IC has typical cystoscopic and histologic features; however, frequently the diagnosis is one of exclusion. IC is diagnosed after the physician has ruled out specific causes, such as urinary infection and malignancy. IC represents an important inflammatory disorder underlying overactive bladder (OAB), which is characterised by increased spontaneous myogenic activity, fused tetanic contractions, altered responsiveness to stimuli, and characteristic changes in smooth muscle ultrastructure. Intravesical botulinum neurotoxin type A (BoNT/A), which has revolutionised the treatment of intractable symptoms associated with the neurogenic or idiopathic OAB, is being increasingly used in BPS/IC [2]. However, its mode of action in the human bladder remains largely unknown. BoNT/A has been found to inhibit the release of a number of neurotransmitters (including acetylcholine, adenosine triphosphate, and neuropeptides such as substance P) and to down-regulate the expression of purinergic and capsaicin receptors on afferent neurons within the bladder. In an experimental model of cyclophosphamide (CYP)-induced cystitis [3] it has been hypothesized that BoNT-A might suppress COX-2 and PGE2 receptor subtype (EP4) expression, reducing the induced bladder hyperactivity and inflammation. Another drug has recently been shown to ameliorate bladder dysfunction through a dual mechanism of action. A vitamin D receptor agonist, elocalcitol, which has well-known efficacy in reducing prostate growth and inflammation [4], inhibited the activation of the RhoA/Rho-kinase pathway (the “calcium sensitization pathway”) in the bladder muscular compartment, reducing spontaneous and inappropriate bladder contractility [5] and [6], and preventing voiding impairment and urinary retention. In conclusion, preclinical studies like these, investigating the effect of current and emerging therapies, acting on the different pathophysiological factors underlying the bladder hyperactivity and inflammation, should be encouraged.