Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats.
OBJECTIVE
We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (NGF-Abs) and desensitization of C-fiber afferent pathways by capsaicin treatment on detrusor-sphincter dyssynergia (DSD) after spinal cord injury (SCI).


METHODS
In adult female rats SCI was induced by complete transection of the spinal cord at Th8 to 9. Ten days after spinalization vehicle or NGF-Ab (10 microg daily) was continuously administered at the level of the L6-S1 spinal cord through an implanted intrathecal catheter connected to an osmotic pump for 2 weeks. Another group of spinalized rats was treated with capsaicin (125 mg/kg subcutaneously) 3 weeks after spinalization and 5 days before experiments. Simultaneous recordings of intravesical pressure and urethral perfusion pressure were then performed. NGF levels in the L6 spinal cord were measured in vehicle or NGF-Ab treated spinalized rats using enzyme-linked immunosorbent assay.


RESULTS
DSD was observed in all vehicle treated spinalized rats. The average urethral pressure increase at the peak bladder contraction was significantly lower by 84% and 78% in NGF-Ab and capsaicin treated spinalized rats, respectively, than in vehicle treated rats. After NGF-Ab treatment NGF levels were significantly decreased by 38% in the L6 spinal cord compared with vehicle treated spinalized rats, in which NGF levels in the L6 spinal cord were 7 times higher than in spinal intact rats.


CONCLUSIONS
Increased levels of NGF in the spinal cord could contribute to the emergence of DSD that is at least in part mediated by C-fiber bladder afferents after SCI. Thus suppression of NGF levels in afferent pathways could be useful for treating DSD following SCI.
Seki
Satoshi
S
Department of Urology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Sasaki
Katsumi
K
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
Chancellor
Michael B
MB
De Groat
William C
WC
Yoshimura
Naoki
N
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001259:Ataxia; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D008159:Lumbar Vertebrae; D009130:Muscle, Smooth / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012447:Sacrum; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D000906:Antibodies; D020932:Nerve Growth Factor; D002211:Capsaicin