Neurotrophins as regulators of urinary bladder function
In this Review, Ochodnicky and colleagues discuss the clinical and experimental evidence that supports a role for neurotrophins in the neural control of bladder function and in the emergence of lower urinary tract symptoms related to overactive bladder (OAB) and bladder pain syndrome/interstitial cy...
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| Published in: | Nature reviews. Urology Vol. 9; no. 11; pp. 628 - 637 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
London
Nature Publishing Group UK
01-11-2012
Nature Publishing Group |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | In this Review, Ochodnicky and colleagues discuss the clinical and experimental evidence that supports a role for neurotrophins in the neural control of bladder function and in the emergence of lower urinary tract symptoms related to overactive bladder (OAB) and bladder pain syndrome/interstitial cystitis. They also consider the potential utility of neurotrophins as urinary biomarkers for improving the accuracy of OAB diagnosis and monitoring therapy efficacy, and review proof-of-principle clinical evidence that confirms nerve growth factor as a potential target in the treatment of bladder disorders.
Increased voiding frequency and urgency are among the most prevalent storage lower urinary tract symptoms (LUTS), often diagnosed as part of overactive bladder syndrome (OAB). It has been suggested that these symptoms are caused by excessive sensory activation of the neural micturition circuit. It seems likely that sensory pathway remodelling is also responsible for pain perception upon bladder filling in patients with bladder pain syndrome (BPS). Neurotrophins—including nerve growth factor (NGF), brain-derived nerve factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4)—represent master modulators of neural plasticity, both in peripheral and central nervous systems. Accumulating evidence points towards a role for neurotrophins in the control of neural sensory function during micturition and indicates their involvement in the emergence of OAB-related and BPS-related LUTS. Neurotrophins could potentially be used as urinary biomarkers to improve diagnostic accuracy for OAB and BPS and monitor therapy effectiveness. Proof-of-principle clinical evidence has confirmed that NGF is a potential target for treating human bladder overactivity.
Key Points
Urgency, frequency and bladder pain are all associated with hypersensitization and remodelling of bladder peripheral afferents
Exogenous administration of nerve growth factor (NGF) to the bladder or spinal cord induces bladder overactivity in experimental animal models
NGF—and possibly brain-derived neurotrophic factor (BDNF)—is produced in the bladder by urothelium and smooth muscle cells upon stretch and inflammation to sensitize underlying bladder afferent C fibres
Peripheral or central NGF sequestration reduces bladder overactivity in experimental models of spinal cord injury, bladder inflammation and outlet obstruction; local NGF delivery improves bladder underactivity in experimental diabetic cystopathy
NGF and BDNF represent potential disease biomarkers for bladder pain syndrome/interstitial cystitis (BPS/IC) and overactive bladder syndrome; increased urinary excretion correlates with symptom severity and can be modulated by therapy
Neurotrophin system intervention using the monoclonal NGF antibody tanezumab has been shown to improve self-reported bladder pain scores and urgency episode frequency in patients with BPS/IC |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 1759-4812 1759-4820 |
| DOI: | 10.1038/nrurol.2012.178 |