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Urodynamic effects of intravenous and intrathecal administration of E‐series prostaglandin 1 receptor antagonist on detrusor overactivity in rats with spinal cord injury
Author(s) -
Wada Naoki,
Kadekawa Katsumi,
Majima Tsuyoshi,
Shimizu Takahiro,
Tyagi Pradeep,
Kakizaki Hidehiro,
Yoshimura Naoki
Publication year - 2018
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.23319
Subject(s) - medicine , spinal cord , spinal cord injury , cystometry , receptor antagonist , anesthesia , receptor , antagonist , prostaglandin e2 , prostaglandin , endocrinology , urinary bladder , psychiatry
Aims We examined the effect of an E‐series prostaglandin 1 (EP1) receptor antagonist on bladder activity using a rat model of spinal cord injury (SCI). Methods Female Sprague‐Dawley rats were used. Six weeks after spinal cord transection, conscious‐filling cystometry was performed. We evaluated the urodynamic parameters before and after intravenous (0.1 and 1.0 mg/kg) or intrathecal (0.1 and 1.0 µg) administration of SC51089, an EP1 antagonist. Spinal prostaglandin E2 (PGE2) concentration and EP1 receptor transcripts in the spinal cord and dorsal root ganglia (DRG) were measured by enzyme‐linked immunosorbent assay and RT‐PCR, respectively. Results The time to the first non‐voiding contraction (NVC) was significantly prolonged after both 0.1 and 1.0 mg/kg of intravenous administration of SC51089 (75% prolongation at 1.0 mg/kg) whereas other parameters were not significantly changed compared to vehicle treatment. In addition, the time to the first NVC was also significantly prolonged after 1.0 µg of intrathecal administration of SC51089 (18% prolongation at 1.0 µg) whereas other parameters were not significantly changed. The spinal PGE2 concentration in SCI rats was significantly higher than that in spinal intact rats. The mRNA expressions of EP1 receptors in the both spinal cord and DRG from SCI rats were significantly higher than those from spinal intact rats. Conclusions The PGE2‐induced activation of EP1 receptors in the spinal cord contributes to the initiation of detrusor overactivity in SCI. Thus, the EP1 receptor could be a therapeutic target for the treatment of neurogenic detrusor overactivity due to SCI.