The ATP-P2X signaling pathway mediates the effect of electroacupuncture on excessive bladder detrusor muscle contraction in a rat model of neurogenic bladder

Abstract

Background:

Neurogenic bladder (NB) is a neurological bladder dysfunction characterized by increased contraction of the detrusor muscle. Adenosine triphosphate (ATP)-P2X receptor signaling influences muscle contraction. The aim of this study was to determine whether ATP-P2X signaling affects the mechanism by which electroacupuncture (EA) influences excessive detrusor muscle contraction in a rat model of NB.

Methods:

Forty-eight rats were divided into CON (n = 8), SHAM (n = 8) and MODEL (n = 32) groups. After the latter group underwent model establishment, 24 successfully modeled rats were randomly divided into the NB, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS; P2X_1/2 receptor antagonist) and EA groups (n = 8 each). The NB model was established using a modified Hassan Shaker spinal cord transection method. One week after EA treatment, urodynamic tests were used to assess bladder function, morphological changes were evaluated in hematoxylin and eosin stained bladder sections, enzyme-linked immunosorbent assays were used to measure ATP concentrations, and Western blotting was used to analyze the protein levels of P2X₁, P2X₂, phosphorylated myosin light chain kinase (p-MLCK) and phosphorylated myosin light chain (p-MLC).

Results:

NB treatment led to morphological abnormalities, impaired urodynamics, increased ATP/P2X₁/P2X₂/p-MLC levels (p < 0.01) and decreased p-MLCK protein levels (p < 0.01). EA treatment significantly improved the morphological abnormalities and impaired urodynamics. Compared with NB, both EA and PPADS significantly reduced ATP/P2X1/P2X2/p-MLC levels (p < 0.01) and increased the expression of p-MLCK (p < 0.01).

Conclusion:

The ATP-P2X signaling pathway may be involved in the mitigating effect of EA on excessive detrusor contractions in this rat model of NB.