Purinergic P2X7 receptors as therapeutic targets in interstitial cystitis/bladder pain syndrome; key role of ATP signaling in inflammation

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic lower urinary tract condition. Patients with IC/BPS suffer from debilitating pain and urinary urgency. The underlying etiology of IC/BPS is unknown and as such current treatments are mostly symptomatic with no real cure. Many theories have been proposed to describe the etiology of IC/BPS, but this review focuses on the role of inflammation. In IC/BPS patients, the permeability of the urothelium barrier is compromised and inflammatory cells infiltrate the bladder wall. There are increased levels of many inflammatory mediators in patients with IC/BPS and symptoms such as pain and urgency that have been associated with the degree of inflammation. Recent evidence has highlighted the role of purinergic receptors, specifically the P2X7 receptor, in the process of inflammation. The results from studies in animals including cyclophosphamide-induced hemorrhagic cystitis strongly support the role of P2X7 receptors in inflammation. Furthermore, the deletion of the P2X7 receptor or antagonism of this receptor significantly reduces inflammatory mediator release from the bladder and improves symptoms. Research results from IC/BPS patients and animal models of IC/BPS strongly support the crucial role of inflammation in the pathophysiology of this painful disease. Purinergic signaling and purinergic receptors, especially the P2X7 receptor, play an undisputed role in inflammation. Purinergic receptor antagonists show positive results in treating different symptoms of IC/BPS.