Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord.
BACKGROUND
Exogenous NGF or saline was delivered to the detrusor smooth muscle of female rats for a two-week period using osmotic mini-pumps. We then determined: (1) bladder function using conscious cystometry; (2) organization of micturition reflexes using Fos protein expression in lumbosacral (L5-S1) spinal cord neurons; (3) calcitonin gene-related peptide (CGRP)-immunoreactivity (IR) in lumbosacral spinal cord segments.


METHODS
An osmotic pump infused 0.9% NaCl (n = 6) or NGF (n = 6)(2.5 microg/microl solution; 0.5 microl/hr) for two weeks into the bladder wall. NGF bladder content was determined by enzyme-linked immunoassays. Bladder function was assessed with conscious cystometry. Immunohistochemical and imaging techniques were used to determine the distribution of Fos-IR cells and CGRP expression in the L5-S1 spinal cord in saline and NGF-treated rats two hours after intravesical saline distention. Fos expression and CGRP-IR in NGF-treated rats with bladder distention was compared to that observed in cyclophosphamide (CYP; 75 mg/kg; i.p.) treated rats with bladder distention.


RESULTS
Two-week infusion of NGF into the bladder wall increased bladder weight, reduced bladder capacity (60%), reduced the intercontraction interval (60%) and increased the amplitude of non-voiding contractions. NGF treatment and intravesical saline distention (2 hr) increased expression of Fos protein in L6-S1 spinal cord and altered the distribution pattern of Fos-IR cells. CGRP-IR in the lumbosacral spinal cord was also increased after NGF treatment.


CONCLUSIONS
These data suggest that NGF infusion into the bladder wall induces bladder overactivity, can reveal a "nociceptive" Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus and increases CGRP-IR in the lumbosacral spinal cord.
Zvara
Peter
P
Department of Surgery, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA. peter.zvara@uvm.edu
Vizzard
Margaret A
MA
D000818:Animals; D005260:Female; D008160:Lumbosacral Plexus / Q000187:drug effects / Q000503:physiopathology; D020932:Nerve Growth Factor; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000139:chemically induced* / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects*
D020932:Nerve Growth Factor