title: Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target.
abstract: In the last two decades, nerve growth factor (NGF), initially described as a prototypical trophic factor in the development of sensory and sympathetic innervation, has emerged as a complex regulator of neural plasticity along the micturition pathways. This review aims to summarize the current experimental and clinical evidence for a role of NGF in urinary bladder. Experimental administration of NGF elicits the states of increased sensation, urgency, and bladder hyperreflexia, resembling pathologies associated with bladder overactivity and inflammatory pain, such as overactive bladder syndrome (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). There is strong experimental evidence, including the effective therapeutic targeting, on the direct causal role of NGF in rodent models of bladder outlet obstruction, spinal cord injury, diabetic bladder dysfunction, and interstitial inflammation. In humans, there are attempts to employ urinary NGF levels as a diagnostic marker in various forms of OAB and IC/PBS. In near future, use of novel experimental tools, such as urothelium-specific NGF transgenic mice or more specific low-molecular weight NGF receptor modulators, may provide better understanding of several unresolved issues in NGF-related bladder dysfunction. Moreover, successful experimental therapeutic approaches, such as NGF sequestering proteins or modified NGF antibodies, await the translation to the clinical treatment of bladder disorders.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. p.ochodnicky@amc.uva.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Ochodnický
authors.forename: Célia D
authors.initials: CD
authors.lastname: Cruz
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D012677:Sensation; D015398:Signal Transduction; D001743:Urinary Bladder / Q000294:innervation*; D001745:Urinary Bladder Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D014563:Urodynamics
chemical_list: D015415:Biomarkers; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA