Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders.
The case is compelling for the involvement of nerve growth factor (NGF) in the pathogenesis of lower urinary tract disease, especially in conditions with altered neural function. Remodeling of the micturition pathways occurs following experimental bladder-outlet obstruction, denervation, spinal cord injury, cystitis, and diabetes mellitus. Clinically, NGF levels are elevated in the bladders of men with benign prostatic hyperplasia, women with interstitial cystitis and in patients with idiopathic overactive bladder. Blockade of NGF, using either an endogenous antibody or an antibody against the NGF receptor, prevents neural plasticity and bladder overactivity in experimental models of these conditions. The ability of NGF to trigger bladder overactivity might rely on altering the properties of sodium or potassium channels (or their expression) in bladder afferent fibers. Therapies based on altered NGF levels, or changes in channel properties in afferent nerves, represent an intriguing avenue of investigation for the management of detrusor overactivity or diabetic cystopathy.
Department of Urology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. wds6t@virginia.edu
William D
WD
Steers
Jeremy B
JB
Tuttle
D006801:Humans; D020932:Nerve Growth Factor / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism; D001743:Urinary Bladder / Q000294:innervation / Q000503:physiopathology; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*
D020932:Nerve Growth Factor