Characterization and restoration of altered inhibitory and excitatory control of micturition reflex in experimental autoimmune encephalomyelitis in rats

Multiple sclerosis (MS) is characterized by inflammatory lesions throughout the central nervous system. Spinal cord inflammation correlates with many neurological defecits. Most MS patients suffer from micturition dysfunction with urinary incontinence and difficulty in emptying the bladder. In exper...

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Veröffentlicht in:The Journal of physiology 2007-01, Vol.578 (2), p.439-450
Hauptverfasser: Vignes, Jean‐Rodolphe, Deloire, Mathilde S. A., Petry, Klaus G., Nagy, Frédéric
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Sprache:eng
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Zusammenfassung:Multiple sclerosis (MS) is characterized by inflammatory lesions throughout the central nervous system. Spinal cord inflammation correlates with many neurological defecits. Most MS patients suffer from micturition dysfunction with urinary incontinence and difficulty in emptying the bladder. In experimental autoimmune encephalomyelitis (EAE) induced in female Lewis rats, a model of MS, we investigated at distinct clinical severity scores the micturition reflex by cystometrograms. All rats presenting symptomatic EAE suffered from micturition reflex alterations with either detrusor areflexia or hyperactivity. During pre-symptomatic EAE, a majority of rats presented with detrusor areflexia, whereas at onset of clinical EAE, detrusor hyperactivity was predominant. During progression of EAE, detrusor areflexia and hyperactivity were equally expressed. Bladder hyperactivity was suppressed by activation of glycine and GABA receptors in the lumbosacral spinal cord with an order of potency: glycine > GABA B > GABA A . Detrusor areflexia was transformed into detrusor hyperactivity by blocking glycine and GABA receptors. Spinalization abolished bladder activity in rats presenting detrusor hyperactivity and failed to induce activity in detrusor areflexia. Altogether, the results reveal an exaggerated descending excitatory control in both detrusor reflex alterations. In detrusor areflexia, a strong segmental inhibition dominates this excitatory control. As in treatment of MS, electrical stimulation of sacral roots reduced detrusor hyperactivity in EAE. Blockade of glycine receptors in the lumbosacral spinal cord suppressed the stimulation-induced inhibitory effect. Our data help to better understand bladder dysfunction and treatment mechanisms to suppress detrusor hyperactivity in MS.
ISSN:0022-3751
1469-7793
DOI:10.1113/jphysiol.2006.117366