Role of P2X3 receptor in dorsal root ganglion in colitis-induced bladder overactivity

Abstract

Objective To investigate the role of P2X3 receptor in dorsal root ganglion (DRG) in bladder micturition function due to colitis-induced bladder dysfunction in the rat model of 2, 4, 6-trinitrosulfonic acid (TNBS)-induced colitis. Methods Female SD rats were randomly divided into control group, TNBS-3d and TNBS-7d groups. The rat model of colitis was induced with 50% TNBS ethanol solution (100 mg/kg) by clyster, and the rats from the control group were clystered by isopyknic normal saline. In 3 or 7 d after clyster, the colon and bladder tissue of rats were collected for HE staining and Nissl Staining. Cystometry was performed to observe the bladder micturition function. Immunofluorescence staining was carried out to detect the expression of P2X3 receptor in DRG. The effect of P2X3 on colitis-induced bladder dysfunction was observed by intrathecal injection of P2X3 receptor inhibitor A-317491. Results The colons of TNBS-induced colitis rats showed mucosal hyperemia and edema and inflammatory cell infiltration. There were no histopathological changes in the bladder among the 3 groups. Compared to the control group, there were larger number of mast cells observed in the bladder from the TNBS-3d and TNBS-7d groups. The results of cystometry showed that the intercontractile interval of bladder (ICI) was significantly decreased and maximum bladder pressure (MBP) was obviously increased in the TNBS-3d group than the control group (P < 0.01). Similarly, the ICI in TNBS-7d group was significantly decreased (P < 0.01), but MBP did not differ from the control group. The number of P2X3 positive neurons in DRG from the TNBS-3d and TNBS-7d groups was increased significantly compared to the control group (P < 0.01). Intrathecal injection of P2X3 inhibitor A-317491 significantly prolonged the interval of micturition (P < 0.01) in the TNBS-3d and TNBS-7d groups and reduced the maximum bladder pressure in TNBS-3d groups (P < 0.05). Conclusion P2X3 receptor in DRG plays an important role in the pathophysiological process of bladder overactivity induced by colitis, and inhibition of P2X3 receptor in DRG may be an effective treatment strategy for the overactive bladder.

Keywords

• p2x3
• colitis
• overactive bladder
• colon-to-bladder cross-sensitization