Afferent nerve regulation of bladder function in health and disease.
The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.
de Groat
William C
WC
Department of Pharmacology, University of Pittsburgh School of Medicine, West 1352 Starzl Biomedical Science Tower, Pittsburgh, PA 15261, USA. degroat@server.pharm.pitt.edu
Yoshimura
Naoki
N
D000200:Action Potentials; D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D003556:Cystitis / Q000378:metabolism / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009473:Neuronal Plasticity; D012018:Reflex; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology; D014524:Urethral Obstruction / Q000378:metabolism / Q000503:physiopathology; D001743:Urinary Bladder / Q000294:innervation*; D001745:Urinary Bladder Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000503:physiopathology
D007473:Ion Channels