Noradrenergic Regulation of Motoneurons Innervating the Urethral Sphincter

Hypothesis / aims of study Duloxetine and reboxetine are two drug that inhibit reuptake of norepinephrine and increase norepinephrine levels in the central nervous system. Both drugs have shown clinical efficacy in the treatment of stress urinary incontinence (1). It is still unclear, however, how increases in norepinephrine can modulate urethral sphincter activity. Spinal motoneurons of Onuf’s nucleus innervate the urethral sphincter through the pudendal nerve. Because the cell somata of these motoneurons are densely innervated by noradrenergic terminals, Onuf’s nucleus represents a putative site of action for reuptake inhibitors (2). Therefore, we hypothesized that elevated levels of norepinephrine due to reuptake inhibition may result in excitation of the motoneurons in Onuf’s nucleus. To test this hypothesis, we studied the direct effects of norepinephrine on the motoneurons using an isolated spinal cord slice preparation.