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Role of p38 MAP kinase signaling pathways in storage and voiding dysfunction in mice with spinal cord injury
Author(s) -
Shimizu Nobutaka,
Wada Naoki,
Shimizu Takahiro,
Suzuki Takahisa,
Kurobe Masahiro,
Kanai Anthony J.,
Groat William C.,
Hashimoto Mamoru,
Hirayama Akihide,
Uemura Hirotsugu,
Yoshimura Naoki
Publication year - 2020
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.24170
Subject(s) - medicine , trpv1 , spinal cord injury , cystometry , anesthesia , spinal cord , nitric oxide synthase , urination , urinary bladder , endocrinology , nitric oxide , urinary system , receptor , transient receptor potential channel , psychiatry
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.