Increased nerve growth factor expression triggers bladder overactivity.
Prior studies have demonstrated an association between visceral inflammation, an increase in nerve growth factor (NGF) expression, and development of hyperalgesia. Because multiple mediators are released during inflammatory processes, we examined the effect of NGF alone using viral gene transfer in vivo. Replication-deficient adenoviral vectors encoding for NGF or beta-galactosidase were injected into the bladder wall. NGF levels were determined with an enzyme-linked immunoabsorbance assay. Cystometrograms were obtained 3 and 5 days after gene transfer by using a surgically implanted bladder catheter in awake male rats. Although the treatment with a control virus did not change NGF levels compared with those of naive animals, the vector encoding for NGF increased NGF protein levels in the bladder 4-fold. Histologically, no evidence of inflammation was noted. Expression of NGF led to bladder overactivity, whereas beta-galactosidase expression was without effect. These data demonstrate that a transient increase in NGF expression without associated inflammation sensitizes visceral reflex pathways, leading to bladder overactivity. Treatment strategies targeting NGF signaling might be useful in disorders involving sensitization of peripheral nerves.


CONCLUSIONS
Growth factors have been implicated in the pathogenesis of inflammatory pain. This study uses gene transfer to demonstrate that NGF sensitizes afferent pathways in the absence of inflammation, making it a potentially relevant treatment target.
Lamb
K
K
Department of Pharmacology, University of Iowa, Iowa City, USA.
Gebhart
G F
GF
Bielefeldt
K
K
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D001750:Urinary Bladder, Neurogenic / Q000209:etiology* / Q000473:pathology; D014546:Urinary Catheterization; D001616:beta-Galactosidase / Q000378:metabolism
D020932:Nerve Growth Factor; D001616:beta-Galactosidase