TY - JOUR
T1 - Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats
AU - Seki, Satoshi
AU - Sasaki, Katsumi
AU - Igawa, Yasuhiko
AU - Nishizawa, Osamu
AU - Chancellor, Michael B.
AU - De Groat, William C.
AU - Yoshimura, Naoki
N1 - Funding Information:
Supported by National Institutes of Health Grants DK 49430, DK 57267 and P01 HD39868.
PY - 2004/1
Y1 - 2004/1
N2 - Purpose: 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). Materials and 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 μg 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.
AB - Purpose: 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). Materials and 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 μg 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.
KW - Bladder
KW - Nerve growth factor
KW - Rats, Sprague-Dawley
KW - Spinal cord injuries
KW - Urethra
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U2 - 10.1097/01.ju.0000088340.26588.74
DO - 10.1097/01.ju.0000088340.26588.74
M3 - Article
C2 - 14665959
AN - SCOPUS:0347479268
VL - 171
SP - 478
EP - 482
JO - Investigative Urology
JF - Investigative Urology
SN - 0022-5347
IS - 1
ER -