Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats

Background: The role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP). Methods: A total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC. Results: The rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-1(ki, CYP-30d, and CYP45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected. Conclusions: P2X3 receptors in dorsal root ganglia (DGR) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.