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. 2004 Jan;171(1):478-82.
doi: 10.1097/01.ju.0000088340.26588.74.

Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats

Satoshi Seki  1 , Katsumi Sasaki, Yasuhiko Igawa, Osamu Nishizawa, Michael B Chancellor, William C De Groat, Naoki Yoshimura
Affiliations

Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats

Satoshi Seki et al. J Urol. 2004 Jan.

Abstract

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 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.

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