Tibial nerve stimulation improves bladder dysfunction after pelvic nerve injury through suppression of the Piezo1/NLRP3 pathway

Liu X1, Lu J2, Li Q3, Wen J3

Research Type

Pure and Applied Science / Translational

Abstract Category

Neurourology

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Abstract 115
Novel Experimental Models
Scientific Podium Short Oral Session 13
Thursday 8th October 2026
10:15 - 10:22
Parallel Hall 4
0.10 Sydney
Capacity: 265
Neuromodulation Animal Study Basic Science Pathophysiology Voiding Dysfunction
1. Xinyang Central Hospital, 2. Henan Medical University, 3. The First Affiliated Hospital of Zhengzhou University
Presenter
X

Xingchen Liu
Xinyang Central Hospital

Links

Abstract

Hypothesis / aims of study
Bladder dysfunction following pelvic nerve injury (PNI) is a common complication after pelvic tumor surgery and remains difficult to treat because its underlying molecular mechanisms are not fully understood. Tibial nerve stimulation (TNS) has shown therapeutic potential in improving lower urinary tract dysfunction, but the precise mechanism remains unclear[1]. Recent evidence suggests that the mechanosensitive ion channel Piezo1 and the NLRP3 inflammasome contribute to bladder inflammation and fibrosis after nerve injury[2-3]. We hypothesized that TNS alleviates PNI-related bladder dysfunction by modulating the Piezo1/NLRP3 signaling pathway.
Study design, materials and methods
Sprague-Dawley rats were randomly assigned to four groups: sham, TNS, PNI, and PNI+TNS (n=8/group). PNI was induced by bilateral pelvic nerve transection. TNS was administered daily for 4 weeks using standardized stimulation parameters. Bladder function was evaluated by urodynamic testing, including bladder capacity, compliance, and voiding pressure. Histological changes were assessed by hematoxylin-eosin and Masson staining. Expression of fibrosis markers and Piezo1/NLRP3 pathway-related proteins, including Piezo1, NLRP3, and IL-1β, was analyzed by Western blot and immunofluorescence.
Results
Compared with the sham and TNS groups, the PNI group showed significant bladder dysfunction on urodynamic testing, characterized by reduced bladder compliance and abnormal voiding pressure. Histological examination revealed marked inflammatory infiltration and collagen deposition in bladder tissue after PNI, whereas these pathological changes were attenuated following TNS treatment. Western blot and immunofluorescence demonstrated low expression of Piezo1, NLRP3, and IL-1β in the sham and TNS groups, significant upregulation in the PNI group, and partial reversal after TNS intervention.
Interpretation of results
PNI-induced mechanical stress activates Piezo1, triggering NLRP3 inflammasome activation and IL-1β release, leading to bladder inflammation, fibrosis, and dysfunction. TNS interrupts this cascade, as evidenced by reduced Piezo1/NLRP3/IL-1β expression and improved urodynamic parameters. These findings suggest that the Piezo1/NLRP3 axis is a critical therapeutic target of TNS.
Concluding message
TNS alleviates PNI-related bladder dysfunction by suppressing the Piezo1/NLRP3 inflammatory pathway, highlighting a potential therapeutic target for neurogenic bladder treatment.
Figure 1 Figure 1. TNS improves bladder function and attenuates bladder fibrosis after pelvic nerve injury.
Figure 2 Figure 2. TNS suppresses PIEZO1/NLRP3/IL-1β pathway activation in bladder tissue after pelvic nerve injury.
References
  1. [1]Li X, Li X, Liao L: Mechanism of Action of Tibial Nerve Stimulation in the Treatment of Lower Urinary Tract Dysfunction. Neuromodulation 2024, 27(2):256-266.
  2. [2]Li X, Hu J, Zhao X, et al. Piezo channels in the urinary system [J]. Exp Mol Med, 2022, 54(6): 697-710.
  3. [3]	Joshi C S, Salazar A M, Wang C, et al. D-Mannose reduces cellular senescence and NLRP3/GasderminD/IL-1ß-driven pyroptotic uroepithelial cell shedding in the murine bladder [J]. Dev Cell, 2024, 59(1): 33-47.e5.
Disclosures
Funding This study was supported by the Science and Technology Research Project of Henan Province (252102310213), the Science and Technology Research Project of Xinyang City(20250086), Young Scientists Fund Project of Henan Provincial Natural Science Foundation (252300423841), and the Henan Academy of Innovations in Medical Science “Three 100” Program—Overseas Training Program for Medical Science and Technology Innovation Talents (H20250330). Clinical Trial No Subjects Animal Species Rat Ethics Committee Ethics Committee of Xinyang Central Hospital AI For simple textual assistance in writing the abstract manuscript
Citation

Continence 19S (2026) 102592
DOI: 10.1016/j.cont.2026.102592

31/10/2026 20:24:44