| Title: |
Nerve growth factor‐dependent hyperexcitability of capsaicin‐sensitive bladder afferent neurones in mice with spinal cord injury |
| Authors: |
Shimizu, Takahiro; Majima, Tsuyoshi; Suzuki, Takahisa; Shimizu, Nobutaka; Wada, Naoki; Kadekawa, Katsumi; Takai, Shun; Takaoka, Eiichiro; Kwon, Joonbeom; Kanai, Anthony J.; de Groat, William C.; Tyagi, Pradeep; Saito, Motoaki; Yoshimura, Naoki |
| Contributors: |
U.S. Department of Defense; National Institute of Diabetes and Digestive and Kidney Diseases |
| Source: |
Experimental Physiology ; volume 103, issue 6, page 896-904 ; ISSN 0958-0670 1469-445X |
| Publisher Information: |
Wiley |
| Publication Year: |
2018 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
New Findings What is the central question of this study ? Nerve growth factor (NGF) is reportedly a mediator inducing urinary bladder dysfunction. Is NGF directly involved in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent pathways after spinal cord injury (SCI)? What is the main finding and its importance ? Neutralization of NGF by anti‐NGF antibody treatment reversed the SCI‐induced increase in the number of action potentials and the reduction in spike thresholds and A‐type K + current density in mouse capsaicin‐sensitive bladder afferent neurones. Thus, NGF plays an important and direct role in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent neurones attributable to the reduction in A‐type K + channel activity in SCI. Abstract Nerve growth factor (NGF) has been implicated as an important mediator in the induction of C‐fibre bladder afferent hyperexcitability, which contributes to the emergence of neurogenic lower urinary tract dysfunction after spinal cord injury (SCI). In this study, we determined whether NGF immunoneutralization using an anti‐NGF antibody (NGF‐Ab) normalizes the SCI‐induced changes in electrophysiological properties of capsaicin‐sensitive C‐fibre bladder afferent neurones in female C57BL/6 mice. The spinal cord was transected at the Th8/Th9 level. Two weeks later, continuous administration of NGF‐Ab (10 μg kg −1 h −1 , s.c . for 2 weeks) was started. Bladder afferent neurones were labelled with 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 neurones were prepared. Whole‐cell patch‐clamp recordings were then performed in FB‐labelled neurones. After recording action potentials or voltage‐gated K + currents, the sensitivity of each neurone to capsaicin was evaluated. In capsaicin‐sensitive FB‐labelled neurones, SCI significantly reduced the spike threshold and increased the number of action potentials during membrane depolarization for 800 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1113/ep086951 |
| DOI: |
10.1113/EP086951 |
| Availability: |
https://doi.org/10.1113/ep086951; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2FEP086951; https://onlinelibrary.wiley.com/doi/pdf/10.1113/EP086951; https://onlinelibrary.wiley.com/doi/full-xml/10.1113/EP086951; https://physoc.onlinelibrary.wiley.com/doi/am-pdf/10.1113/EP086951; https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/EP086951 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#am ; http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.171FE55A |
| Database: |
BASE |