GAP-43 immunoreactivity of subepithelial and detrusor muscle nerve fibres in patients with refractory idiopathic detrusor overactivity.
OBJECTIVE
To determine the relative density of nerve fibres immunoreactive to growth associated protein-43 (GAP-43, an indicator of neuronal sprouting) in the subepithelium and detrusor of patients with idiopathic detrusor overactivity (IDO). To investigate the effect, if any, of age and previous recurrent bacterial cystitis on neuronal sprouting in such patients.


METHODS
A series of 18 women with urodynamically proven IDO (median age 62 years, range 39-85), who were refractory to treatment, underwent cystoscopy and cold cup biopsy. Controls (n=26, median age 65, range 32-79) were females without urgency/urge incontinence, undergoing cystoscopy for other indications. Recurrent proven bacterial cystitis (rUTI) was documented. Frozen sections were stained with specific antibodies to GAP-43 and protein gene product 9.5 (PGP, a general neuronal marker). The area represented by immunoreactive (ir) subepithelial or muscle nerve fibres was measured.


RESULTS
The density of GAP-43ir and PGPir nerves did not differ significantly between IDO patients and controls, in either subepithelium or detrusor. The GAP-43ir nerve density (as percent of PGPir) increased significantly with advancing age amongst patients with IDO in the detrusor muscle but not in the subepithelium; density in controls was unaltered. In IDO patients with rUTI, a significant increase in GAP-43 (as percent of PGPir) was observed in the subepithelium.


CONCLUSIONS
Although we found no evidence of increased neuronal proliferation in patients with IDO generally, the increase in GAP-43 with age and with previous cystitis history suggests that neuronal sprouting is important in some subsets of patients with IDO.
Schofield
E C
EC
The Detrusor Muscle Laboratory, Department of Urogynaecology, St. George Hospital, University of New South Wales, Sydney, Australia.
Clausen
J A
JA
Burcher
E
E
Moore
K H
KH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology; D003556:Cystitis / Q000382:microbiology; D003558:Cystoscopy; D004351:Drug Resistance; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000382:microbiology; D009130:Muscle, Smooth / Q000294:innervation* / Q000503:physiopathology; D009412:Nerve Fibers / Q000378:metabolism* / Q000473:pathology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D001743:Urinary Bladder / Q000294:innervation* / Q000382:microbiology / Q000473:pathology; D001745:Urinary Bladder Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014552:Urinary Tract Infections / Q000378:metabolism / Q000503:physiopathology; D014563:Urodynamics / Q000502:physiology
D019922:GAP-43 Protein; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase