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Intravesical nerve growth factor antisense therapy for bladder hypersensitivity induced by psychological stress
Tetsuichi Saito1,2, Pradeep Tyagi1, Tomonori Minagawa2
1Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gene Therapy
|September 2, 2024
Summary
Psychological stress causes bladder hypersensitivity by increasing nerve growth factor (NGF). Antisense oligonucleotide (ASO) therapy targeting NGF effectively improved stress-induced bladder dysfunction in rats.
Area of Science:
- Urology
- Neuroscience
- Pharmacology
Background:
- Psychological stress can induce bladder hypersensitivity and dysfunction.
- Nerve growth factor (NGF) is implicated in bladder sensory pathways.
Purpose of the Study:
- To investigate the role of NGF in psychological stress-induced bladder hypersensitivity.
- To evaluate the therapeutic potential of NGF antisense oligonucleotide (ASO) therapy in a rat model.
Main Methods:
- Water avoidance stress (WAS) model in female Wistar rats.
- Intravesical administration of NGF ASO to modulate NGF expression.
- Functional assessments including cystometry and pain behavior measurements.
- Histological and molecular analyses of bladder tissue.
Main Results:
- WAS induced bladder hypersensitivity, characterized by shorter intercontraction intervals and increased pain behaviors.
- NGF levels, TRPV1, and TRPA1 expression were upregulated in WAS rat bladders.
- NGF ASO treatment significantly ameliorated WAS-induced bladder dysfunction and molecular changes.
- Low-dose protamine sulfate induced urothelial exfoliation in WAS rats.
Conclusions:
- NGF upregulation in the bladder contributes to psychological stress-induced bladder hypersensitivity.
- NGF antisense oligonucleotide therapy represents a promising therapeutic strategy for stress-related bladder dysfunction.
