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Piezo2 in sensory neurons contributes to inflammation-induced bladder overactivity and is associated with the effects of electroacupuncture
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DOI：10.3389/fnins.2026.1886563.png)
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Abstract
En 中文
ObjectivesTo assess the effects of varying doses of cyclophosphamide (CYP) on lower urinary tract function in rats; and to further investigate the role of Piezo2 in sensory neurons in a CYP-induced interstitial cystitis/bladder pain syndrome (IC/BPS) model and its potential as a therapeutic target for electroacupuncture (EA).MethodsLower urinary tract function was assessed by employing cystometry; external urethral sphincter electromyography; and void spot assay. Bladders were harvested for histological observation. L6-S1 dorsal root ganglia were collected for detection of Piezo2 expression by RNAscope; immunofluorescence staining; and Western blotting. L6-S1 spinal cords were harvested for c-Fos immunofluorescence staining to evaluate activation of spinal neurons.ResultsFive days subsequent to the completion of administration with 50; 60; and 75 mg/kg CYP; bladder function in rats still had not returned to baseline levels. However; the 40 mg/kg dose only caused a reduction in the area under the curve of pressure traces; indicating a change in bladder contractility. Administration with 75 mg/kg CYP did not induce a more severe bladder phenotype than 60 mg/kg CYP. Intrathecal injection of antisense oligonucleotides to knockdown Piezo2 expression in sensory neurons ameliorated bladder overactivity and urethral hyperreflexia in rats with CYP-induced IC/BPS; accompanied by lessened activation of spinal neurons. Aside from that; EA improves lower urinary tract function in rats with cystitis; which may be associated with the downregulation of Piezo2 expression in sensory neurons and the lessened activation of spinal neurons.ConclusionPiezo2 in sensory neurons contributes to inflammation-induced bladder overactivity and is associated with the effects of EA. Collectively; targeted inhibition of Piezo2 expression and function may represent a promising novel strategy for managing inflammatory bladder dysfunction; with these data also shedding preliminary light on how EA exerts its therapeutic effects in this condition. On top of that; our study provides novel insights into the characteristics of the CYP-induced IC/BPS model and the establishment of a rat void spot assay protocol.
Keywords:
Piezo2
electroacupuncture
sensory neuron
interstitial cystitis/bladder pain syndrome
void spot assay
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