MP42-03 EFFECTS OF NERVE GROWTH FACTOR NEUTRALIZATION ON HYPEREXCITABILITY OF CAPSAICIN SENSITIVE BLADDER AFFERENT NEURONS IN MICE WITH SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2017MP42-03 EFFECTS OF NERVE GROWTH FACTOR NEUTRALIZATION ON HYPEREXCITABILITY OF CAPSAICIN SENSITIVE BLADDER AFFERENT NEURONS IN MICE WITH SPINAL CORD INJURY Takahiro Shimizu, Tsuyoshi Majima, Takahisa Suzuki, Nobutaka Shimizu, Naoki Wada, Shun Takai, Eiichiro Takaoka, Joonbeom Kwon, Pradeep Tyagi, Motoaki Saito, and Naoki Yoshimura Takahiro ShimizuTakahiro Shimizu More articles by this author , Tsuyoshi MajimaTsuyoshi Majima More articles by this author , Takahisa SuzukiTakahisa Suzuki More articles by this author , Nobutaka ShimizuNobutaka Shimizu More articles by this author , Naoki WadaNaoki Wada More articles by this author , Shun TakaiShun Takai More articles by this author , Eiichiro TakaokaEiichiro Takaoka More articles by this author , Joonbeom KwonJoonbeom Kwon More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Motoaki SaitoMotoaki Saito More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1292AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nerve growth factor (NGF) has been implicated as an important mediator to induce C-fiber bladder afferent hyperexcitability, which contributes to the emergence of neurogenic detrusor overactivity (NDO) following spinal cord injury (SCI). In this study, we examined whether NGF neutralization using anti-NGF antibody normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fiber bladder afferent neurons in the mouse model. METHODS In female C57BL/6 mice, the spinal cord was transected at the Th8/9 level. Two weeks later, an osmotic pump was placed subcutaneously to administer anti-NGF antibody at 10 µg/kg/h for 2 weeks. Bladder afferent neurons were labeled with axonal transport of Fast Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6-S1 dorsal root ganglion neurons were prepared. Whole cell patch clamp recordings were then performed in FB-labeled bladder afferent neurons, and the data were compared between SCI and spinal intact (SI) mice. After recording action potentials (AP) or voltage-gated K+ (Kv) currents, the sensitivity of each neuron to capsaicin was evaluated. RESULTS In capsaicin-sensitive bladder afferent neurons, the resting membrane potentials and the peak and duration of AP did not changed by SCI. On the other hand, the threshold for eliciting AP was significantly reduced in SCI vs. SI mice. Also, SCI increased the number of AP during 800 ms membrane depolarization. These SCI induced changes were reversed by NGF neutralization. SCI induced significant increases in the diameter and cell input capacitance of capsaicin-sensitive bladder afferent neurons, which were not reversed by NGF neutralization. Densities of slow decaying KA and sustained KDR currents evoked by depolarization to 0 mV were significantly reduced by SCI. NGF neutralization reversed the SCI-induced reduction in the KA current density. CONCLUSIONS In SCI mice, NGF plays an important role in hyperexcitability of capsaicin sensitive C-fiber bladder afferent neurons due to KA current reduction. Thus, NGF-targeting therapies could be effective for treatment of afferent hyperexcitability and NDO in SCI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e544-e545 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Takahiro Shimizu More articles by this author Tsuyoshi Majima More articles by this author Takahisa Suzuki More articles by this author Nobutaka Shimizu More articles by this author Naoki Wada More articles by this author Shun Takai More articles by this author Eiichiro Takaoka More articles by this author Joonbeom Kwon More articles by this author Pradeep Tyagi More articles by this author Motoaki Saito More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...