Submitted on March 26, 2008
Revised on May 5, 2008
Accepted on May 21, 2008
SUPPRESSION OF DETRUSOR-SPHINCTER DYSYNERGIA BY GABA-RECEPTOR ACTIVATION IN THE LUMBOSACRAL SPINAL CORD IN SPINAL CORD INJURED RATS
MINORU Miyazato, KURUMI SASATOMI, SHIRO HIRAGATA, KIMIO Sugaya1, MICHAEL B. Chancellor, WILLIAM C de Groat, and NAOKI Yoshimura2*
1 UNIVERSITY OF THE RYUKYUS
2 University of Pittsburgh
* To whom correspondence should be addressed. E-mail: nyos{at}pitt.edu.
We investigated the effects of intrathecal application of GABAA or GABAB receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 weeks after Th9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABAA and GABAB agonists (muscimol and baclofen, respectively) or GABAA and GABAB antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. In spinal intact rats, the effects of bicuculline and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions was observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal intact rats, intrathecal application of bicuculline induced DSD-like changes. These results indicate that GABAA and GABAB receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABAA receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible at least in part for the development of DSD after SCT.
