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Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity
Byron W Hayes1, Hae Woong Choi2, Abhay P S Rathore1,3
1Department of Pathology, Duke University Medical Center, Durham, NC, USA.
Science Immunology
|March 1, 2024
Summary
Recurrent urinary tract infections (rUTIs) cause chronic bladder pain and urinary frequency due to nerve growth factor (NGF)-driven nerve sprouting and mast cell activation, not active infection.
Area of Science:
- Urology
- Neuroscience
- Immunology
Background:
- Recurrent urinary tract infections (rUTIs) cause persistent bladder symptoms like pain and frequency.
- These symptoms often persist after antibiotic treatment, suggesting non-bacterial causes.
Purpose of the Study:
- To investigate the mechanisms behind bacteria-independent bladder symptoms in rUTI patients.
- To identify potential therapeutic targets for chronic pelvic pain and urinary dysfunction in rUTI.
Main Methods:
- Examined bladder tissue from rUTI patients for neuropeptide changes.
- Induced rUTI in mice to study sensory nerve sprouting and mast cell involvement.
- Utilized nerve growth factor (NGF)-neutralizing antibodies and mast cell antagonists in mouse models.
Main Results:
- Increased neuropeptide content and nociceptive activity observed in rUTI patient bladders.
- rUTI mice showed sensory nerve sprouting linked to NGF from monocytes and mast cells.
- NGF neutralization prevented nerve sprouting and pain; NGF instillation mimicked symptoms.
- Mast cell activation was crucial for nerve activation, pain, and urinary frequency.
Conclusions:
- NGF-driven sensory nerve sprouting, coupled with mast cell activation, underlies bacteria-independent pain and urinary dysfunction in rUTI.
- Targeting NGF and mast cell pathways offers potential therapeutic strategies for rUTI symptoms.
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