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- Title
Role of p38 MAP kinase signaling pathways in storage and voiding dysfunction in mice with spinal cord injury.
- Authors
Shimizu, Nobutaka; Wada, Naoki; Shimizu, Takahiro; Suzuki, Takahisa; Kurobe, Masahiro; Kanai, Anthony J.; Groat, William C.; Hashimoto, Mamoru; Hirayama, Akihide; Uemura, Hirotsugu; Yoshimura, Naoki
- Abstract
Aim: To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI). Methods: Cystometry and external urethral sphincter‐electromyography were performed under an awake condition in 4‐week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen‐activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6‐S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 μL/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor‐treated SCI mice as well as from CSF‐treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor‐α (TNF‐α), and inducible nitric oxide synthase (iNOS) transcripts by real‐time polymerase chain reaction. Results: In p38 MAPK inhibitor‐treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post‐void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF‐treated SCI mice. The expression of TRPV1, TNF‐α, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment. Conclusions: The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.
- Subjects
MITOGEN-activated protein kinases; SPINAL cord injuries; TRP channels; URINATION disorders; DORSAL root ganglia
- Publication
Neurourology & Urodynamics, 2020, Vol 39, Issue 1, p108
- ISSN
0733-2467
- Publication type
Academic Journal
- DOI
10.1002/nau.24170