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J Physiol Volume 578, Number 2, 439-450, January 15, 2007 DOI: 10.1113/jphysiol.2006.117366
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NEUROSCIENCE

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

Jean-Rodolphe Vignes1, Mathilde S. A. Deloire2, Klaus G. Petry2 and Frédéric Nagy1

1 INSERM E358, Institute François Magendie; University Bordeaux 2, 146 rue Léo Saignat, 33077 Bordeaux Cedex, France
2 University Bordeaux 2, EA2966, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France

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 > GABAB > GABAA. 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.

(Received 17 July 2006; accepted after revision 15 October 2006; first published online 26 October 2006)
Corresponding author F. Nagy: INSERM E358, Institut François Magendie, Université Bordeaux 2, 146 rue Léo Saignat, 33077 Bordeaux Cedex, France. Email: frederic.nagy{at}bordeaux.inserm.fr


K. G. Petry and F. Nagy contributed equally to this work.







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