This paper aims at evaluating the role of serotonin (5-HT) and noradrenaline in the nervous control of urinary continence. Both α1-adrenergic and 5-HT2 receptors in the Onuf's nucleus help the guarding reflex; therefore the pharmacologic agents enhancing the effects of 5-HT and noradrenaline represent a promising choice in treating stress urinary incontinence. Duloxetine, a dual 5-HT/noradrenaline reuptake inhibitor, improves the external urethral sphincter contractility while increasing the activation of 5-HT2 and α1-adrenergic receptors thanks to the high concentrations of these monoamines in the Onuf's nucleus; it also plays a significant role in the management of stress urinary incontinence.
AbramsP., CardozoL., FallM.The standardisation of terminology in lower urinary function: report from the standardisation sub-committee of the International Continence Society. Urology2003; 61: 37–49.
2.
AbramsP., BlaivasJ.G., StantonS.L., AndersenJ.T.The standardisation of terminology of lower urinary tract function. The International Continence Society Committee on Standardisation of terminology. Scand J Urol Nephrol1998; 114(suppl.): S5–19.
3.
ThomD.Variation in estimates of urinary incontinence prevalence in the community: effects of differences in definition, population, characteristics and study type. J Am Geriatric Soc1998; 46: 473–80.
4.
JonasU.Stress urinary incontinence in women: introduction and conclusions. Eur Urol2005; 4(suppl.): 1–4.
5.
ChancellorM.B., PerkinH., YoshimuraN.Recent advances in neurophysiology of IUS. Scand J Urol Nephrol2005; 39: 21–24.
6.
BlokB.F.M., OlstegeG.The central control of micturition and continence: implications for urology. BJU International, 1999; 83(suppl. 2): S1–6.
7.
ThorK.B., DonatucciC.Central nervous system control of the lower urinary tract. J Urol2004; 172: 27–3.
BlokB.F.M., WillemsenA.T.M., HolstegeG.A PET study on brain control of micturition in humans. Brain1997; 120: 111–21.
10.
FraserM.O., ChancellorM.B.Neural control of the urethra and development of pharmacotherapy for stress urinary incontinence. BJU International, 2003; 91: 743–8.
11.
AnderssonK.E.New pharmacologic targets for the treatment of overactive bladder: an update. Urology2004; 63(suppl. 3A): S32–41.
ViktrupL., PangalloB.A., DetkeM.J., ZinnerN.R.Urinary side effects in the treatment of depression and SUI. J Clin Psychiatry2004; 6: 65–73.
14.
HeldoornM., Van LeeuwenJ.L., VanderschootJ., MaraniE.Electrotonic coupling in a network of compartmental external urethral sphincter motoneurons of Onuf's nucleus. Neurocomputing2001; 38: 647–58.
15.
ThorK.B.Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdomiosphincter: implications for treating stress urinary incontinence. Urology2003; 62(suppl. 4A), S3–9.
16.
AnderssonK-E. Change in bladder tone during filling: pharmacological aspects. Scan J Urol Nephrol1999: 201: 67–72.
17.
de GroatW.X.Anatomy of the central neuron pathways controlling the lower urinary tract. Eur Urol1998; 34(suppl. 1): S2–5.
18.
KoliatsosV.E., SheltonD.L., MobleyW.C.A novel group of nerve growth factor receptor-immunoreactive neurons in the ventral horn of the lumbar spinal cord. Brain Res1991; 541: 121–8.
19.
HeltonL.A., ThorK.B., BaezM.5-HT2A, 5-HT2B, 5-HT2C receptor mRNA expression in the spinal cord of rat, cat, monkey and human. Neuroreport1994; 5: 2617–20.
20.
de GroatW.C., KawataniW., HisamitsuT.The role of neuropeptides in the sacral autonomic pathways of the cat. J Auton Nerv Syst1983; 7: 339–50.
ThorK.B., KatofiascM.A.Effects of duloxetine, a combined 5-HT and noradrenaline reuptake inhibitor on central neural control of lower urinary tract function in chlorolose-anesthetized female cat. J Pharmacol Exp Ther1995: 274: 1014–24.
25.
KatofiascM.A., NissenJ., AudiaJ.E., ThorK.B.Comparison of the effects of serotonin selective, norepinephrine selective and dual serotonin and norepinephrine reuptake inhibitors on lower tract function in cats. Life Sci2002: 71: 1227–35.
26.
DmochowskiR.R., MiklosJ.R., NortonP.A., ZinnerN.R., YaldinI., BumpR.C.Duloxetine versus placebo for the treatment of north american women with stress urinary incontinence. J Urol2003; 170: 1259–63.
WongD.T., BymasterF.R., MayleD.A., ReidL.R., KrushinskiJ.H., RobertsonD.W.LY248686; a new inhibitor of serotonin and noepinephrine uptake. Neuropsychopharmacology1993; 8(suppl. I): S23–33.
29.
AndrewsJ.M., NinanP.T., NemeroffC.B.Venlafaxine: a novel antidepressant that has a dual mechanism of action. Depression1996; 4: 48–56.
30.
GehlertD.R., Hemrick-LueckeS.K., SchoberD.A., KrushinskiJ., HowbertJ.J., RobertsonD.W.Thionisoxetine, a potent and selective inhibitor of central and peripheral norepinephrine uptake. Life Sci1995; 1915–20.
31.
SteersW., CorcosJ., FooteJ., KralidisG.An investigation of dose titration with darifenacin, an M3-selective receptor antagonist. BJU International, 2005; 955580–6.
32.
LazzeriM., BenefortiP., SpinelliM., ZanolloA., BargagliG., TuriniD.Intravescical resiniferatoxin for the treatment of hypersensitive disorder. J Urol2000; 164: 676–9.
33.
KuoH.C.Multiple intravescical instillation of low-dose resiniferatoxin is effective in the treatment of detrusor overactivity refractory to anticholinergics. BJU International2005; 95: 1023–7.
34.
Chartier-KastlerE.SUI: current management and unmet needs. Eur Urol2005; suppl 4: 11–17.
35.
KerrebroeckP., AbramsP., LangeR., SlackM., WyndaeleJ-J, YalcinI.Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. Br J Obstet Gynaecol2004; 111: 249–57.
36.
ZinnerN.R.Stress urinary incontinence in women. Efficacy and safety of duloxetine. Eur Urol2005; suppl 4: 29–37.
37.
Van KerrebroeckP.Duloxetine: an innovative approach for treating stress urinary incontinence. BJU Intern2004; 94(suppl. 1): S31–7.
38.
YalcinI., BumpR.C.Validation of two global impression questionnaires for incontinence. Am J Obstet Gynecol2003; 189: 98–101.
39.
MillardR.J., MooreK., RenckenR., YalcinI., BumpR.C.Duloxetine versus placebo in the treatment of stress urinary incontinence: a four continent randomized clinical trial. BJU International2004; 93: 311–8.
40.
MichelM.C., PetersS.L.M.Role of serotonin and N-adrenaline in stress urinary incontinence. BJU International2004; 94(suppl. 1): S23–30.
41.
LeachG.E., DmochowskiR.R., AppellR.A., BlavaisJ.G., HadleyH.R., LuberK.Femal SUI: clinical guidelines summary report in surgical management. Am Urol Ass J Urol1997; 158(3 Pt 1), 875–80.
42.
ArtibaniW., GrassiD., PesceF.Incontinenza urinaria. Min Urol Nefrol1999; 51(suppl. 1): S1–5.
DioknoA.C., BurgioK., FutzH., KinchenK.H., ObenchainR., BumpR.C.Prevalence and outcomes of continence surgery in community dwelling women. J Urol2003; 170: 507–511.
GhoniemG.M., vanLeeuwenJ.S., ElserD.M.I.A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment in women with stress urinary incontinence. J Urol2005; 173: 1647–53.
48.
LeeJ.Y., CannonT.W., PruchnicR.Periurethral muscle-derived stem cell injection on rat model of IUS. Int Urogynecol pelvic Floor Dysfunct2003; 14: 31–7.
