• Neurourol. Urodyn. · Aug 2018

    The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury.

    • Naoki Wada, Takahiro Shimizu, Nobutaka Shimizu, William C de Groat, Anthony J Kanai, Pradeep Tyagi, Hidehiro Kakizaki, and Naoki Yoshimura.
    • Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
    • Neurourol. Urodyn. 2018 Aug 1; 37 (6): 1889-1896.

    AimsTo investigate the role of nerve growth factor (NGF) in lower urinary tract dysfunction in mice with spinal cord injury (SCI).MethodsUsing 4-week SCI mice, single-filling cystometry and external urethral sphincter (EUS)-electromyography were performed under an awake condition. In some SCI mice, anti-NGF antibodies (10 µg/kg/h) were administered for 1 or 2 weeks before the urodynamic study. NGF levels in the bladder and L6/S1 spinal cord were assayed by ELISA. The transcript levels of P2X receptors and TRP channels in L6/S1 dorsal root ganglia (DRG) were measured by RT-PCR.ResultsIn SCI mice, the area under the curve of non-voiding contractions (NVCs) during the storage phase was significantly decreased in both 1- and 2-week anti-NGF antibody-treated SCI groups. However, EUS-electromyogram parameters during voiding were not altered by the treatment. Bladder mucosal and spinal NGF levels were decreased after 2 weeks of anti-NGF antibody treatment. TRPA1 and TRPV1 transcripts in L6/S1 DRG were significantly decreased after 1- or 2-week anti-NGF treatment.ConclusionsIn SCI mice, NGF is involved in the emergence of NVCs in association with increased expression of TRP receptors that are predominantly found in C-fiber afferent pathways. Thus, NGF targeting treatments could be effective for treating storage problems such as detrusor overactivity after SCI.© 2018 Wiley Periodicals, Inc.

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