Electroacupuncture relives overactive bladder symptoms by modulating the generation and transduction of Piezo1 channel mediated mechanosensory signals in the urothelium

Hu J1, Li X1, Tang K2, Song Q3, Liu J2, Chen Y1

Research Type

Pure and Applied Science / Translational

Abstract Category

Research Methods / Techniques

Abstract 773
Open Discussion ePosters
Scientific Open Discussion Session 108
Friday 25th October 2024
13:10 - 13:15 (ePoster Station 4)
Exhibition Hall
Animal Study Conservative Treatment Overactive Bladder Bladder Outlet Obstruction Neuromodulation
1. Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China, 2. Shanghai University of Traditional Chinese Medicine, Shanghai, China, 3. Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Presenter
Links

Poster

Abstract

Hypothesis / aims of study
EA has been found to be an effective treatment of OAB , but its mechanisms of action remain unclear. This study aims to reveal the modulatory mechanisms of EA on Piezo1 channel mediated sensitivity of the urothelium in an OAB rat model.
Study design, materials and methods
EA stimulation was applied to OAB rat model, followed by bladder functional assessments. The urothelial Piezo1 mechanical stretching sensory signal molecules and its afferent nerve transduction pathways were investigated to explore the mechanism of EA in the treatment of OAB .Eighteen female SD rats (7-week-old, 220-230g) were randomly divided into Sham partial bladder outlet obstruction (PBOO) group, PBOO group and PBOO&EA group. The EA treatment consisted of one week of needling in bilateral Ciliao (Located in the 2nd posterior sacral foramen) and Huiyang acupoint (located at anteromedial of the transverse process of the 6th lumbar spine). The EA-induced bladder functional changes were assessed by voiding spots test and urodynamic study. The morphological changes of the bladder mucosal layer were evaluated by HE staining. The expression of c-Fos in L6-S1 segments of, and P2X3 in dorsal root ganglion were detected by WB, qRT-PCR and immunofluorescence. Calcium imaging was used to measure Ca2+ concentration in the urothelial cells. The ATP content in the urine of rats was detected by ELISA. Afferent nerve signals were observed by pelvic nerve recording, and external urethral sphincter electrical activity was observed by electromyography recording.
Results
Compared with the Sham PBOO group, the number of urine spots in the PBOO group was increased during 3 hours of observation, with decreased average urine volume, shortened voiding interval, and reduced voiding threshold pressure. The PBOO group also demonstrated significantly increased Piezo1expression in the urothelium, along with increased intracellular Ca2+ concentration and urine ATP content. Simultaneously, the afferent nerve action potential was significantly increased, the external urethral sphincter electromyography was intensified during voiding, and the expression of c-Fos in the spinal cord of L6-S1 segments and P2X3 in DRG was increased after OAB induction. After one week of EA treatment, the functional indices of bladder storage phase in OAB rats were significantly improved, with no significant difference compared with sham PBOO group. In addition, EA significantly reduced the expression of urothelial Piezo1 and the release of ATP in the urine, as well as inhibited the transmission of excitatory signals from the pelvic nerve to the spinal cord level.
Interpretation of results
The therapeutic effects of EA on relieving storage symptoms is possibly achieved by downregulating Piezo1 expression, inhibiting Ca2+ influx, and reducing ATP release. Meanwhile, the decreased pelvic nerve action potential and excitatory neurotransmitters in the spinal segments, suggesting that EA treatment provides not only reginal effects at peripheral organ, but also inhibition of central sensory input.
Concluding message
EA significantly relieved OAB symptoms in a rat model, possibly through downregulating urothelial Piezo1 expression and attenuating its downstream mechanosensory signals from pelvic nerve to the dorsal root of spinal segment to minimize excitatory afferent inputs.
Disclosures
Funding National Natural Science Foundation of China (No. 82174516); National Natural Science Foundation of China (No. 82270819); National Key R&D Program of China(No. 2023YFC3606001) Clinical Trial No Subjects Animal Species Rat Ethics Committee Animal Experiment Ethics Committee of Shanghai University of Traditional Chinese Medicine
20/11/2024 04:38:32