Premium
Nerve growth factor‐dependent hyperexcitability of capsaicin‐sensitive bladder afferent neurones in mice with spinal cord injury
Author(s) -
Shimizu Takahiro,
Majima Tsuyoshi,
Suzuki Takahisa,
Shimizu Nobutaka,
Wada Naoki,
Kadekawa Katsumi,
Takai Shun,
Takaoka Eiichiro,
Kwon Joonbeom,
Kanai Anthony J.,
Groat William C.,
Tyagi Pradeep,
Saito Motoaki,
Yoshimura Naoki
Publication year - 2018
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep086951
Subject(s) - capsaicin , nerve growth factor , spinal cord , dorsal root ganglion , urinary bladder , spinal cord injury , endocrinology , medicine , chemistry , neuroscience , anesthesia , biology , receptor
New FindingsWhat 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 ms. These SCI‐induced changes were reversed by NGF‐Ab. Densities of slow‐decaying A‐type K + (K A ) and sustained delayed rectifier‐type K + currents were significantly reduced by SCI. The NGF‐Ab treatment reversed the SCI‐induced reduction in the K A current density. These results indicate that NGF plays an important role in hyperexcitability of mouse capsaicin‐sensitive C‐fibre bladder afferent neurones attributable to a reduction in K A channel activity. Thus, NGF‐targeting therapies could be effective for treatment of afferent hyperexcitability and neurogenic lower urinary tract dysfunction after SCI.