Neural control of the female urethral and anal rhabdosphincters and pelvic floor muscles

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 299, Issue 2, 2010, Pages

  Thor, Karl B ^a   De Groat, William C ^b  

^a ASTELLAS PHARMA INC   (Japan)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

Defecation; Incontinence; Micturition; Pelvic organ prolapse; Urethra

Indexed keywords

ANUS SPHINCTER; BLADDER SPHINCTER; HUMAN; LEVATOR ANI MUSCLE; MICTURITION; MOTONEURON; NEUROCHEMISTRY; NONHUMAN; PELVIC ORGAN PROLAPSE; PELVIS FLOOR; PRIORITY JOURNAL; REVIEW; SENSORY NERVE;

ANAL CANAL; ANIMALS; DEFECATION; FEMALE; HUMANS; MOTOR NEURONS; NEURAL INHIBITION; NEURONS, AFFERENT; PARTURITION; PELVIC FLOOR; PELVIC ORGAN PROLAPSE; PHENOTYPE; REFLEX; SENSATION; URETHRA; URINARY INCONTINENCE; URINATION;

EID: 77955503575     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00111.2010     Document Type: Review

References (204)

1. Allen RE, Hosker GL, Smith AR, Warrell DW. Pelvic floor damage and childbirth: a neurophysiological study. Br J Obstet Gynaecol 97: 770-779, 1990.
2. Arvidsson U, Risling M, Frisen J, Piehl F, Fried K, Hokfelt T, Cullheim S. trkC-Like immunoreactivity in the primate descending serotoninergic system. Eur J Neurosci 6: 230-236, 1994.
3. Ashton-Miller JA, DeLancey JO. Functional anatomy of the female pelvic floor. Ann NY Acad Sci 1101: 266-296, 2007.
4. Barber MD, Bremer RE, Thor KB, Dolber PC, Kuehl TJ, Coates KW. Innervation of the female levator ani muscles. Am J Obstet Gynecol 187: 64-71, 2002.
5. Beattie MS, Li Q, Leedy MG, Bresnahan JC. Motoneurons innervating the external anal and urethral sphincters of the female cat have different patterns of dendritic arborization. Neurosci Lett 111: 69-74, 1990.
6. Bernabe J, Julia-Guilloteau V, Denys P, Chartier-Kastler E, Alexandre L, Peeters M, Giuliano F. Peripheral neural lesion-induced stress urinary incontinence in anaesthetized female cats. BJU Int 102: 1162-1167, 2008.
7. Blanco CE, Popper P, Micevych P. α-CGRP mRNA levels in motoneurons innervating specific rat muscles. Brain Res Mol Brain Res 44: 253-261, 1997.
8. Blok BF, de Weerd H, Holstege G. The pontine micturition center projects to sacral cord GABA immunoreactive neurons in the cat. Neurosci Lett 233: 109-112, 1997.
9. Blok BF, Roukema G, Geerdes B, Holstege G. Location of external anal sphincter motoneurons in the sacral cord of the female domestic pig. Neurosci Lett 216: 203-206, 1996.
10. Blok BF, van Maarseveen JT, Holstege G. Electrical stimulation of the sacral dorsal gray commissure evokes relaxation of the external urethral sphincter in the cat. Neurosci Lett 249: 68-70, 1998.
11. Boers J, Ford TW, Holstege G, Kirkwood PA. Functional heterogeneity among neurons in the nucleus retroambiguus with lumbosacral projections in female cats. J Neurophysiol 94: 2617-2629, 2005.
12. Borghi F, Di Molfetta L, Garavoglia M, Levi AC. Questions about the uncertain presence of muscle spindles in the human external anal sphincter. Panminerva Med 33: 170-172, 1991.
13. Bors E, Blinn K Bulbocavernosus reflex. J Urol 82: 128-130, 1959.
14. Boy S, Reitz A, Wirth B, Knapp PA, Braun PM, Haferkamp A, Schurch B. Facilitatory neuromodulative effect of duloxetine on pudendal motor neurons controlling the urethral pressure: a functional urodynamic study in healthy women. Eur Urol 50: 119-125, 2006.
15. Bradley WE, Teague CT. Electrophysiology of pelvic and pudendal nerves in the cat. Exp Neurol 35: 378-393, 1972.
16. Bremer RE, Barber MD, Coates KW, Dolber PC, Thor KB. Innervation of the levator ani and coccygeus muscles of the female rat. Anat Rec A Discov Mol Cell Evol Biol 275: 1031-1041, 2003.
17. Brook GA, Schmitt AB, Nacimiento W, Weis J, Schroder JM, Noth J. Distribution of B-50(GAP-43) mRNA and protein in the normal adult human spinal cord. Acta Neuropathol (Berl) 95: 378-386, 1998.
18. Brown A, Fyffe R. The morphology of group Ia afferent fibre collaterals in the spinal cord of the cat. J Physiol 274: 111-127, 1978.
19. Brown AG, Fyffe RE. The morphology of group Ib afferent fibre collaterals in the spinal cord of the cat. J Physiol 296: 215-226, 1979.
20. Burgard EC, Portbury S, Thor KB. Electrophysiology of motor neurons innervating the urethral sphincter of female rats (Abstract). Proc Soc Neurosci 2008 Annual Meeting, abstract 582.8.
21. Chang HY, Cheng CL, Chen JJ, de Groat WC. Roles of glutamatergic and serotonergic mechanisms in reflex control of the external urethral sphincter in urethane-anesthetized female rats. Am J Physiol Regul Integr Comp Physiol 291: R224-R234, 2006.
22. Chang HY, Cheng CL, Chen JJ, de Groat WC. Serotonergic drugs and spinal cord transections indicate that different spinal circuits are involved in external urethral sphincter activity in rats. Am J Physiol Renal Physiol 292: F1044-F1053, 2007.
23. Chang HY, Cheng CL, Chen JJ, Peng CW, de Groat WC. Reflexes evoked by electrical stimulation of afferent axons in the pudendal nerve under empty and distended bladder conditions in urethane-anesthetized rats. J Neurosci Methods 150: 80-89, 2006.
24. Charlton CG, Helke CJ. Autoradiographic localization and characterization of spinal cord substance P binding sites: high densities in sensory, autonomic, phrenic, and Onuf's motor nuclei. J Neurosci 5: 1653-1661, 1985.
25. Chen GD, Peng HY, Tung KC, Cheng CL, Chen YJ, Liao JM, Ho YC, Pan SF, Chen MJ, Lin TB. Descending facilitation of spinal NMDA-dependent reflex potentiation from pontine tegmentum in rats. Am J Physiol Renal Physiol 293: F1115-F1122, 2007.
26. Chen Z, Anderson DL, Faison WL, Baer PG. Biphasic urethral sphincter responses to acetic acid infusion into the lower urinary tract in anesthetized cats. J Urol 166: 1539-1548, 2001.
27. Cheng CL, de Groat WC. The role of capsaicin-sensitive afferent fibers in the lower urinary tract dysfunction induced by chronic spinal cord injury in rats. Exp Neurol 187: 445-454, 2004.
28. Coates KW, Galan HL, Shull BL, Kuehl TJ. The squirrel monkey: an animal model of pelvic relaxation. Am J Obstet Gynecol 172: 588-593, 1995.
29. 2C-mediated mechanisms involved in urethral sphincter reflexes (Abstract). Proc Soc Neurosci 2005 Annual Meeting, abstract 48.14.
30. Corona-Quintanilla DL, Castelan F, Fajardo V, Manzo J, Martinez- Gomez M. Temporal coordination of pelvic and perineal striated muscle activity during micturition in female rabbits. J Urol 181: 1452-1458, 2009.
31. Creed KE, Van Der Werf BA, Kaye KW. Innervation of the striated muscle of the membranous urethra of the male dog. J Urol 159: 1712-1716, 1998.
32. Cuevas E, Camacho M, Alvarado M, Hudson R, Pacheco P. Participation of estradiol and progesterone in the retrograde labeling of pubococcygeus motoneurons of the female rat. Neuroscience 140: 1435-1442, 2006.
33. Danuser H, Bemis K, Thor KB. Pharmacological analysis of the noradrenergic control of central sympathetic and somatic reflexes controlling the lower urinary tract in the anesthetized cat. J Pharmacol Exp Ther 274: 820-825, 1995.
34. 1 adrenergic receptor antagonist prazosin. J Urol 153: 1308-1312, 1995.
35. 2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat. Br J Pharmacol 118: 150-154, 1996.
36. de Groat WC, Fraser MO, Yoshiyama M, Smerin S, Tai C, Chancellor MB, Yoshimura N, Roppolo JR. Neural control of the urethra. Scand J Urol Nephrol Suppl 207: 35-43; discussion 106-125, 2001.
37. Dietz HP, Wilson PD. Childbirth and pelvic floor trauma. Best Pract Res Clin Obstet Gynaecol 19: 913-924, 2005.
38. Dmochowski RR, Miklos JR, Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence. J Urol 170: 1259-1263, 2003.
39. 1A receptor agonist in rats with chronic spinal cord injury. Am J Physiol Regul Integr Comp Physiol 292: R1699-R1706, 2007.
40. 5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature. J Comp Neurol 476: 316-329, 2004.
41. 7 receptor in rat dorsal spinal cord: immunocytochemical evidence. J Comp Neurol 490: 256-269, 2005.
42. Dorschner W, Biesold M, Schmidt F, Stolzenburg JU. The dispute about the external sphincter and the urogenital diaphragm. J Urol 162: 1942-1945, 1999.
43. Downie JW, Bialik GJ. Evidence for a spinal site of action of clonidine on somatic and viscerosomatic reflex activity evoked on the pudendal nerve in cats. J Pharmacol Exp Ther 246: 352-358, 1988.
44. 2-Adrenoceptors not imidazole receptors mediate depression of a sacral spinal reflex in the cat. Eur J Pharmacol 195: 301-304, 1991.
45. Elbadawi A, Schenk EA. A new theory of the innervation of bladder musculature. 2. Innervation of the vesicourethral junction and external urethral sphincter. J Urol 111: 613-615, 1974.
46. Enck P, Vodusek DB. Electromyography of pelvic floor muscles. J Electromyogr Kinesiol 16: 568-577, 2006.
47. Fajardo V, Pacheco P, Hudson R, Jimenez I, Martinez-Gomez M. Differences in morphology and contractility of the bulbospongiosus and pubococcygeus muscles in nulliparous and multiparous rabbits. Int Urogynecol J Pelvic Floor Dysfunct 19: 843-849, 2008.
48. Fedirchuk B, Hochman S, Shefchyk SJ. An intracellular study of perineal and hindlimb afferent inputs onto sphincter motoneurons in the decerebrate cat. Exp Brain Res 89: 511-516, 1992.
49. Fedirchuk B, Song L, Downie JW, Shefchyk SJ. Spinal distribution of extracellular field potentials generated by electrical stimulation of pudendal and perineal afferents in the cat. Exp Brain Res 89: 517-520, 1992.
50. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci 9: 453-466, 2008.
51. 2-adrenoceptors and glutamate mechanisms in the external urethral sphincter continence reflex in rats. J Urol 181: 1467-1473, 2009.
52. Gajewski J, Downie JW, Awad SA. Experimental evidence for a central nervous system site of action in the effect of α-adrenergic blockers on the external urinary sphincter. J Urol 132: 403-409, 1984.
53. Gerrits PO, Sie JA, Holstege G. Motoneuronal location of the external urethral and anal sphincters: a single and double labeling study in the male and female golden hamster. Neurosci Lett 226: 191-194, 1997. (Pubitemid 27201976)
54. Gibson SJ, Polak JM, Katagiri T, Su H, Weller RO, Brownell DB, Holland S, Hughes JT, Kikuyama S, Ball J, Bloom SR, Steiner TJ, de Belleroche J, Clifford Rose F. A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus. Brain Res 474: 255-278, 1988.
55. Glazer EJ, Basbaum AI. Leucine enkephalin: localization in and axoplasmic transport by sacral parasympathetic preganglionic neurons. Science 208: 1479-1481, 1980.
56. Gonzalez-Soriano J, Martin-Palacios S, Rodriguez-Veiga E, Triguero D, Costa G. Garcia-Pascual A. Nitric oxide synthase in the external urethral sphincter of the sheep: immunohistochemical and functional study. J Urol 169: 1901-1906, 2003.
57. Gosling JA, Dixon JS, Critchley HO, Thompson SA. A comparative study of the human external sphincter and periurethral levator ani muscles. Br J Urol 53: 35-41, 1981.
58. Grigorescu BA, Lazarou G, Olson TR, Downie SA, Powers K, Greston WM, Mikhail MS. Innervation of the levator ani muscles: description of the nerve branches to the pubococcygeus, iliococcygeus, and puborectalis muscles. Int Urogynecol J Pelvic Floor Dysfunct 19: 107-116, 2008.
59. Gu B, Fraser MO, Thor KB, Dolber PC. Induction of bladder sphincter dyssynergia by κ-2 opioid receptor agonists in the female rat. J Urol 171: 472-477, 2004.
60. Gu B, Olejar KJ, Reiter JP, Thor KB, Dolber PC. Inhibition of bladder activity by 5-hydroxytryptamine1 serotonin receptor agonists in cats with chronic spinal cord injury. J Pharmacol Exp Ther 310: 1266-1272, 2004.
61. Gu B, Thor KB, Reiter JP, Dolber PC. Effect of 5-hydroxytryptamine1 serotonin receptor agonists on noxiously stimulated micturition in cats with chronic spinal cord injury. J Urol 177: 2381-2385, 2007.
62. Ho KM, Borja MC, Persson K, Brading AF, Andersson KE. Expression of nitric oxide synthase immunoreactivity in the human female intramural striated urethral sphincter. J Urol 169: 2407-2411, 2003.
63. Ho KM, McMurray G, Brading AF, Noble JG, Ny L, Andersson KE. Nitric oxide synthase in the heterogeneous population of intramural striated muscle fibres of the human membranous urethral sphincter. J Urol 159: 1091-1096, 1998.
64. Holmes GM. 5-Hydroxytryptamine2C receptors on pudendal motoneurons innervating the external anal sphincter. Brain Res 1057: 65-71, 2005.
65. Holmes GM, Rogers RC, Bresnahan JC, Beattie MS. Differential effects of intrathecal thyrotropin-releasing hormone (TRH) on perineal reflexes in male rats. Physiol Behav 61: 57-63, 1997.
66. Holstege G, Griffiths D, de Wall H, Dalm E. Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat. J Comp Neurol 250: 449-461, 1986.
67. Holstege G, Tan J. Supraspinal control of motoneurons innervating the striated muscles of the pelvic floor including urethral and anal sphincters in the cat. Brain 110: 1323-1344, 1987.
68. Holstege JC, Van Dijken H, Buijs RM, Goedknegt H, Gosens T, Bongers CM. Distribution of dopamine immunoreactivity in the rat, cat and monkey spinal cord. J Comp Neurol 376: 631-652, 1996.
69. Hounsgaard J, Hultborn H, Jespersen B, Kiehn O. Bistability of α-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan. J Physiol 405: 345-367, 1988.
70. Hounsgaard J, Kiehn O. Serotonin-induced bistability of turtle motoneurones caused by a nifedipine-sensitive calcium plateau potential. J Physiol 414: 265-282, 1989.
71. Hurtado EA, Smith PP, Smith CP, Boone TB, Somogyi GT. Urethral afferent signaling leads to activation of the external urethral sphincter and abdominal wall muscles. Neurourol Urodyn 27: 105, 2008.
72. Jankowska E, Padel Y, Zarzecki P. Crossed disynaptic inhibition of sacral motoneurones. J Physiol 285: 425-444, 1978.
73. Kaiho Y, Nishiguchi J, Kwon DD, Chancellor MB, Arai Y, Snyder PB, Yoshimura N. The effects of a type 4 phosphodiesterase inhibitor and the muscarinic cholinergic antagonist tolterodine tartrate on detrusor overactivity in female rats with bladder outlet obstruction. BJU Int 101: 615-620, 2008.
74. Kamo I, Torimoto K, Chancellor MB, de Groat WC, Yoshimura N. Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence. Am J Physiol Regul Integr Comp Physiol 285: R356-R365, 2003.
75. 1A receptors in female cats. Am J Physiol Regul Integr Comp Physiol 298: R1198-R1208, 2010.
76. Kawatani M, Nagel J, de Groat WC. Identification of neuropeptides in pelvic and pudendal nerve afferent pathways to the sacral spinal cord of the cat. J Comp Neurol 249: 117-132, 1986.
77. Kawatani M, Suzuki T, de Groat WC. Corticotropin releasing factor-like immunoreactivity in afferent projections to the sacral spinal cord of the cat. J Auton Nerv Syst 61: 218-226, 1996.
78. Kenton K, Brubaker L. Relationship between levator ani contraction and motor unit activation in the urethral sphincter. Am J Obstet Gynecol 187: 403-406, 2002.
79. Kim RJ, Kerns JM, Liu S, Nagel T, Zaszczurynski P, Lin DL, Damaser MS. Striated muscle and nerve fascicle distribution in the female rat urethral sphincter. Anat Rec (Hoboken) 290: 145-154, 2007.
80. Kimura Y, Hamada K, Taniguchi N, Ukai Y, Yoshikuni Y, Kimura K. CNS-mediated influence of TRH and its analog, NS-3, on the function of the rabbit lower urinary tract. J Auton Nerv Syst 60: 1-11, 1996.
81. Klarskov N, Scholfield D, Soma K, Darekar A, Mills I, Lose G. Evaluation of the sensitivity of urethral pressure reflectometry and urethral pressure profilometry to detect pharmacological augmentation of urethral pressure using [S,S]-reboxetine. J Urol 179: 521-522, 2008.
82. Koerber HR, Brown PB. Somatotopic organization of hindlimb cutaneous nerve projections to cat dorsal horn. J Neurophysiol 48: 481-489, 1982.
83. Kojima M, Matsuura T, Kimura H, Nojyo Y, Sano Y. Fluorescence histochemical study on the noradrenergic control to the anterior column of the spinal lumbosacral segments of the rat and dog, with special reference to motoneurons innervating the perineal striated muscles (Onuf's nucleus). Histochemistry 81: 237-241, 1984.
84. Kojima M, Takeuchi Y, Goto M, Sano Y. Immunohistochemical study on the distribution of serotonin fibers in the spinal cord of the dog. Cell Tissue Res 226: 477-491, 1982.
85. Kojima M, Takeuchi Y, Goto M, Sano Y. Immunohistochemical study on the localization of serotonin fibers and terminals in the spinal cord of the monkey (Macaca fuscata). Cell Tissue Res 229: 23-36, 1983. (Pubitemid 13154925)
86. Koliatsos VE, Price DL, Clatterbuck RE. Motor neurons in Onuf's nucleus and its rat homologues express the p75 nerve growth factor receptor: sexual dimorphism and regulation by axotomy. J Comp Neurol 345: 510-527, 1994.
87. Konishi A, Itoh K, Sugimoto T, Yasui Y, Kaneko T, Takada M, Mizuno N. Leucine-enkephalin-like immunoreactive afferent fibers to pudendal motoneurons in the cat. Neurosci Lett 61: 109-113, 1985.
88. Kramer LA, Gendron JM, Pierce LM, Runge VM, Shull BL, Kuehl TJ. Magnetic resonance imaging of the levator ani in the squirrel monkey: a comparison of muscle volume between a cohort with pelvic organ prolapse and matched normals. Am J Obstet Gynecol 194: 1467-1471, 2006.
89. Krier J, Thor KB, de Groat WC. Effects of clonidine on the lumbar sympathetic pathways to the large intestine and urinary bladder of the cat. Eur J Pharmacol 59: 47-53, 1979.
90. Kruse MN, Belton AL, de Groat WC. Changes in bladder and external urethral sphincter function after spinal cord injury in the rat. Am J Physiol Regul Integr Comp Physiol 264: R1157-R1163, 1993.
91. Kruse MN, Mallory BS, Noto H, Roppolo JR, de Groat WC. Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat. Brain Res 556: 6-12, 1991.
92. Kuipers R, Izhar Z, Gerrits PO, Miner W, Holstege G. Location of bladder and urethral sphincter motoneurons in the male guinea pig (Cavia porcellus). Neurosci Lett 362: 57-60, 2004.
93. Lee RH, Heckman CJ. Bistability in spinal motoneurons in vivo: systematic variations in persistent inward currents. J Neurophysiol 80: 583-593, 1998.
94. Lee RH, Heckman CJ. Bistability in spinal motoneurons in vivo: systematic variations in rhythmic firing patterns. J Neurophysiol 80: 572-582, 1998.
95. Leung PY, Johnson CS, Wrathall JR. Comparison of the effects of complete and incomplete spinal cord injury on lower urinary tract function as evaluated in unanesthetized rats. Exp Neurol 208: 80-91, 2007.
96. Lewinter RD, Skinner K, Julius D, Basbaum AI. Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat. J Comp Neurol 470: 400-408, 2004.
97. Leyson JF, Martin BF, Sporer A. Baclofen in the treatment of detrusor-sphincter dyssynergia in spinal cord injury patients. J Urol 124: 82-84, 1980.
98. Liao JM, Huang PC, Pan SF, Chen MJ, Tung KC, Peng HY, Shyu JC, Liou YM, Chen GD, Lin TB. Spinal glutamatergic NMDA-dependent pelvic nerve-to-external urethra sphincter reflex potentiation caused by a mechanical stimulation in anesthetized rats. Am J Physiol Renal Physiol 292: F1791-F1801, 2007.
99. Lin SY, Chen GD, Liao JM, Pan SF, Chen MJ, Chen JC, Peng HY, Ho YC, Huang PC, Lin JJ, Lin TB. Estrogen modulates the spinal N-methyl-D-aspartic acid-mediated pelvic nerve-to-urethra reflex plasticity in rats. Endocrinology 147: 2956-2963, 2006.
100. Lin TB. Dynamic pelvic-pudendal reflex plasticity mediated by glutamate in anesthetized rats. Neuropharmacology 44: 163-170, 2003.
101. Lin TB. Tetanization-induced pelvic-to-pudendal reflex plasticity in anesthetized rats. Am J Physiol Renal Physiol 287: F245-F251, 2004.
102. Mackel R. Segmental and descending control of the external urethral and anal sphincters in the cat. J Physiol 294: 105-122, 1979.
103. MacLennan AJ, Devlin BK, Neitzel KL, McLaurin DL, Anderson KJ, Lee N. Regulation of ciliary neurotrophic factor receptor-α in sciatic motor neurons following axotomy. Neuroscience 91: 1401-1413, 1999.
104. Mallory B, Steers WD, deGroat WC. Electrophysiological study of micturition reflexes in rats. Am J Physiol Regul Integr Comp Physiol 257: R410-R421, 1989.
105. Mallory BS, Roppolo JR, de Groat WC. Pharmacological modulation of the pontine micturition center. Brain Res 546: 310-320, 1991.
106. Mantyh PW, Allen CJ, Rogers S, DeMaster E, Ghilardi JR, Mosconi T, Kruger L, Mannon PJ, Taylor IL, Vigna SR. Some sensory neurons express neuropeptide Y receptors: potential paracrine inhibition of primary afferent nociceptors following peripheral nerve injury. J Neurosci 14: 3958-3968, 1994.
107. Manzo J, Esquivel A, Hernandez ME, Carrillo P, Martinez-Gomez M, Pacheco P. The role of pubococcygeus muscle in urinary continence in the male rat. J Urol 157: 2402-2406, 1997.
108. Martin WD, Fletcher TF, Bradley WE. Innervation of feline perineal musculature. Anat Rec 180: 15-29, 1974.
109. 2 receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat. Br J Pharmacol, 2008.
110. McKenna K, Nadelhaft I. The pudendo-pudendal reflex in male and female rats. J Auton Nerv Syst 27: 67-77, 1989.
111. McKenna KE, Nadelhaft I. The organization of the pudendal nerve in the male and female rat. J Comp Neurol 248: 532-549, 1986.
112. McMahon SB, Morrison JF, Spillane K. An electrophysiological study of somatic and visceral convergence in the reflex control of the external sphincters. J Physiol 328: 379-387, 1982.
113. Millard RJ, Moore K, Rencken R, Yalcin I, Bump RC. Duloxetine vs placebo in the treatment of stress urinary incontinence: a four-continent randomized clinical trial. BJU Int 93: 311-318, 2004. (Pubitemid 38253575)
114. Miller AD, Nonaka S, Siniaia MS, Jakus J. Multifunctional ventral respiratory group: bulbospinal expiratory neurons play a role in pudendal discharge during vomiting. J Auton Nerv Syst 54: 253-260, 1995.
115. Mirilas P, Skandalakis JE. Urogenital diaphragm: an erroneous concept casting its shadow over the sphincter urethrae and deep perineal space. J Am Coll Surg 198: 279-290, 2004.
116. Miyazato M, Kaiho Y, Kamo I, Chancellor MB, Sugaya K, de Groat WC, Yoshimura N. Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, on sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol 295: F264-F271, 2008.
117. Miyazato M, Kaiho Y, Kamo I, Kitta T, Chancellor MB, Sugaya K, Arai Y, de Groat WC, Yoshimura N. Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats. Am J Physiol Renal Physiol 297: F1024-F1031, 2009.
118. Miyazato M, Sasatomi K, Hiragata S, Sugaya K, Chancellor MB, de Groat WC, Yoshimura N. GABA receptor activation in the lumbosacral spinal cord decreases detrusor overactivity in spinal cord injured rats. J Urol 179: 1178-1183, 2008.
119. Nacimiento W, Topper R, Fischer A, Mobius E, Oestreicher AB, Gispen WH, Nacimiento AC, Noth J, Kreutzberg GW. B-50 (GAP- 43) in Onuf's nucleus of the adult cat. Brain Res 613: 80-87, 1993.
120. Nadelhaft I, deGroat WC, Morgan C. Location and morphology of parasympathetic preganglionic neurons in the sacral spinal cord of the cat revealed by retrograde axonal transport of horseradish peroxidase. J Comp Neurol 193: 265-281, 1980.
121. Nadelhaft I, Vera PL. Neurons in the rat brain and spinal cord labeled after pseudorabies virus injected into the external urethral sphincter. J Comp Neurol 375: 502-517, 1996.
122. Nakagawa S. Onuf's nucleus of the sacral cord in a South American monkey (Saimiri): its location and bilateral cortical input from area 4. Brain Res 191: 337-344, 1980.
123. Nanninga JB, Frost F, Penn R. Effect of intrathecal baclofen on bladder and sphincter function. J Urol 142: 101-105, 1989.
124. Norton PA, Zinner NR, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of stress urinary incontinence. Am J Obstet Gynecol 187: 40-48, 2002.
125. Ogier R, Tribollet E, Suarez P, Raggenbass M. Identified motoneurons involved in sexual and eliminative functions in the rat are powerfully excited by vasopressin and tachykinins. J Neurosci 26: 10717-10726, 2006.
126. Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL. Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 89: 501-506, 1997.
127. Onufrowicz B. On the arrangement and function of the cell groups of the sacral region of the spinal cord in man. Arch Neurol Psychopathol 3: 387-411, 1900.
128. Pacheco P, Camacho MA, Garcia LI, Hernandez ME, Carrillo P, Manzo J. Electrophysiological evidence for the nomenclature of the pudendal nerve and sacral plexus in the male rat. Brain Res 763: 202-208, 1997.
129. Pacheco P, Martinez-Gomez M, Whipple B, Beyer C, Komisaruk BR. Somato-motor components of the pelvic and pudendal nerves of the female rat. Brain Res 490: 85-94, 1989.
130. Palmieri G, Panu R, Asole A, Sanna L, Farina V. Coccygeus and levator ani muscles in the rabbit: morphology and proprioceptive innervation. Biol Struct Morphog 1: 142-146, 1988.
131. Paroschy KL, Shefchyk SJ. Non-linear membrane properties of sacral sphincter motoneurones in the decerebrate cat. J Physiol 523: 741-753, 2000.
132. Pierce LM, Coates KW, Kramer LA, Bradford JC, Thor KB, Kuehl TJ. Effects of bilateral levator ani nerve injury on pelvic support in the female squirrel monkey. Am J Obstet Gynecol 198: 585.e1-585.e8, 2008.
133. Pierce LM, Rankin MR, Foster RT, Dolber PC, Coates KW, Kuehl TJ, Thor KB. Distribution and immunohistochemical characterization of primary afferent neurons innervating the levator ani muscle of the female squirrel monkey. Am J Obstet Gynecol 195: 987-996, 2006.
134. Pierce LM, Reyes M, Thor KB, Dolber PC, Bremer RE, Kuehl TJ, Coates KW. Immunohistochemical evidence for the interaction between levator ani and pudendal motor neurons in the coordination of pelvic floor and visceral activity in the squirrel monkey. Am J Obstet Gynecol 192: 1506-1515, 2005.
135. Pierce LM, Reyes M, Thor KB, Dolber PC, Bremer RE, Kuehl TJ, Coates KW. Innervation of the levator ani muscles in the female squirrel monkey. Am J Obstet Gynecol 188: 1141-1147, 2003.
136. Praud C, Sebe P, Mondet F, Sebille A. The striated urethral sphincter in female rats. Anat Embryol (Berl) 207: 169-175, 2003.
137. Pullen AH, Humphreys P. Protracted elevation of neuronal nitric oxide synthase immunoreactivity in axotomised adult pudendal motor neurons. J Anat 194: 547-565, 1999.
138. Pullen AH, Humphreys P, Baxter RG. Comparative analysis of nitric oxide synthase immunoreactivity in the sacral spinal cord of the cat, macaque and human. J Anat 191: 161-175, 1997.
139. Rajaofetra N, Passagia JG, Marlier L, Poulat P, Pellas F, Sandillon F, Verschuere B, Gouy D, Geffard M, Privat A. Serotoninergic, noradrenergic, and peptidergic innervation of Onuf's nucleus of normal and transected spinal cords of baboons (Papio papio). J Comp Neurol 318: 1-17, 1992.
140. Ramage AG, Wyllie MG. A comparison of the effects of doxazosin and terazosin on the spontaneous sympathetic drive to the bladder and related organs in anaesthetized cats. Eur J Pharmacol 294: 645-650, 1995.
141. Rampal G, Mignard P. Behaviour of the urethral striated sphincter and of the bladder in the chronic spinal cat. Implications at the central nervous system level. Pflügers Arch 353: 33-42, 1975.
142. Rampal G, Mignard P. Organization of the nervous control of urethral sphincter. A study in the anaesthetized cat with intact central nervous system. Pflügers Arch 353: 21-31, 1975.
143. Ranson RN, Dodds AL, Smith MJ, Santer RM, Watson AH. Age-associated changes in the monoaminergic innervation of rat lumbosacral spinal cord. Brain Res 972: 149-158, 2003.
144. Reitz A, Bretscher S, Knapp P, Müntener M, Wefer B, Schurch B. The effect of nitric oxide on the resting tone and the contractile behaviour of the external urethral sphincter: a functional urodynamic study in healthy humans. Eur Urol 45: 367-373, 2004. (Pubitemid 38221412)
145. Rockswold GL, Bradley WE, Chou SN. Innervation of the external urethral and external anal sphincters in higher primates. J Comp Neurol 193: 521-528, 1980.
146. Roppolo JR, Nadelhaft I, de Groat WC. The organization of pudendal motoneurons and primary afferent projections in the spinal cord of the rhesus monkey revealed by horseradish peroxidase. J Comp Neurol 234: 475-488, 1985.
147. Sasaki M. Morphological analysis of external urethral and external anal sphincter motoneurones of cat. J Comp Neurol 349: 269-287, 1994.
148. Schroder HD. Somatostatin in the caudal spinal cord: an immunohistochemical study of the spinal centers involved in the innervation of pelvic organs. J Comp Neurol 223: 400-414, 1984.
149. Schroder HD, Reske-Nielsen E. Fiber types in the striated urethral and anal sphincters. Acta Neuropathol (Berl) 60: 278-282, 1983.
150. Schwindt PC, Crill WE. Properties of a persistent inward current in normal and TEA-injected motoneurons. J Neurophysiol 43: 1700-1724, 1980.
151. Sebe P, Fritsch H, Oswald J, Schwentner C, Lunacek A, Bartsch G, Radmayr C. Fetal development of the female external urinary sphincter complex: an anatomical and histological study. J Urol 173: 1738-1742, 2005.
152. Sebe P, Schwentner C, Oswald J, Radmayr C, Bartsch G, Fritsch H. Fetal development of striated and smooth muscle sphincters of the male urethra from a common primordium and modifications due to the development of the prostate: an anatomic and histologic study. Prostate 62: 388-393, 2005.
153. Shefchyk SJ. Spinal mechanisms contributing to urethral striated sphincter control during continence and micturition: "how good things might go bad." Prog Brain Res 152: 85-95, 2006.
154. Shefchyk SJ, Espey MJ, Carr P, Nance D, Sawchuk M, Buss R. Evidence for a strychnine-sensitive mechanism and glycine receptors involved in the control of urethral sphincter activity during micturition in the cat. Exp Brain Res 119: 297-306, 1998.
155. Sie JA, Blok BF, de Weerd H, Holstege G. Ultrastructural evidence for direct projections from the pontine micturition center to glycine-immunoreactive neurons in the sacral dorsal gray commissure in the cat. J Comp Neurol 429: 631-637, 2001.
156. Smith AR, Hosker GL, Warrell DW. The role of partial denervation of the pelvic floor in the aetiology of genitourinary prolapse and stress incontinence of urine. A neurophysiological study. Br J Obstet Gynaecol 96: 24-28, 1989.
157. Snooks SJ, Setchell M, Swash M, Henry MM. Injury to innervation of pelvic floor sphincter musculature in childbirth. Lancet 2: 546-550, 1984.
158. Snooks SJ, Swash M, Henry MM, Setchell M. Risk factors in child-birth causing damage to the pelvic floor innervation. Int J Colorectal Dis 1: 20-24, 1986.
159. Snooks SJ, Swash M, Mathers SE, Henry MM. Effect of vaginal delivery on the pelvic floor: a 5-year follow-up. Br J Surg 77: 1358-1360, 1990.
160. South MM, Stinnett SS, Sanders DB, Weidner AC. Levator ani denervation and reinnervation 6 months after childbirth. Am J Obstet Gynecol 200: 519.e1-519.e7, 2009.
161. Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev 81: 209-237, 2001.
162. Steers WD, Meythaler JM, Haworth C, Herrell D, Park TS. Effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary dysfunction due to spinal cord pathology. J Urol 148: 1849-1855, 1992.
163. Tashiro T, Satoda T, Matsushima R, Mizuno N. Convergence of serotonin-, enkephalin- and substance P-like immunoreactive afferent fibers on single pudendal motoneurons in Onuf's nucleus of the cat: a light microscope study combining the triple immunocytochemical staining technique with the retrograde HRP-tracing method. Brain Res 481: 392-398, 1989. (Pubitemid 19064309)
164. Teague CT, Merrill DC. Effect of baclofen and dantrolene on bladder stimulator-induced detrusor-sphincter dyssynergia in dogs. Urology 11: 531-535, 1978.
165. Thor KB. Targeting serotonin and norepinephrine receptors in stress urinary incontinence. Int J Gynaecol Obstet 86 Suppl 1: S38-S52, 2004.
166. Thor KB, Hisamitsu T, Roppolo JR, Tuttle P, Nagel J, deGroat WC. Selective inhibitory effects of ethylketocyclazocine on reflex pathways to the external urethral sphincter of the cat. J Pharmacol Exp Ther 248: 1018-1025, 1989.
167. Thor KB, Katofiasc MA. Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat. J Pharmacol Exp Ther 274: 1014-1024, 1995.
168. Thor KB, Katofiasc MA, Danuser H, Springer J, Schaus JM. The role of 5-HT1A receptors in control of lower urinary tract function in cats. Brain Res 946: 290-297, 2002.
169. Thor KB, Langdale C, Ukai M, Karicheti V. Characterization of a Spinal Urine Storage Reflex Inhibitory Center (SUSRIC) and its regulation by 5-HT1A receptors (Abstract). Proc Society for Neuroscience 2008 Annual Meeting, abstract 582.1.
170. Thor KB, Morgan C, Nadelhaft I, Houston M, de Groat WC. Organization of afferent and efferent pathways in the pudendal nerve of the female cat. J Comp Neurol 288: 263-279, 1989.
171. Thor KB, Muhlhauser MA. Vesicoanal, urethroanal, and urethrovesical reflexes initiated by lower urinary tract irritation in the rat. Am J Physiol Regul Integr Comp Physiol 277: R1002-R1012, 1999.
172. Thor KB, Nickolaus S, Helke CJ. Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/ 2 binding sites in the rat spinal cord. Neuroscience 55: 235-252, 1993.
173. Thor KB, Roppolo JR, Kawatani M, Erdman S, deGroat WC. Plasticity in spinal opioid control of lower urinary tract function in paraplegic cats. Neuroreport 5: 1673-1678, 1994.
174. Thuroff JW, Bazeed MA, Schmidt RA, Luu DH, Tanagho EA. Regional topography of spinal cord neurons innervating pelvic floor muscles and bladder neck in the dog: a study by combined horseradish peroxidase histochemistry and autoradiography. Urol Int 37: 110-120, 1982.
175. Todd JK. Afferent impulses in the pudendal nerves of the cat. Q J Exp Physiol Cogn Med Sci 49: 258-267, 1964.
176. Ueyama T, Arakawa H, Mizuno N. Central distribution of efferent and afferent components of the pudendal nerve in rat. Anat Embryol (Berl) 177: 37-49, 1987.
177. Ueyama T, Mizuno N, Nomura S, Konishi A, Itoh K, Arakawa H. Central distribution of afferent and efferent components of the pudendal nerve in cat. J Comp Neurol 222: 38-46, 1984.
178. Ulibarri C, Popper P, Micevych PE. Motoneurons dorsolateral to the central canal innervate perineal muscles in the Mongolian gerbil. J Comp Neurol 356: 225-237, 1995.
179. 2 receptor in rat spinal cord identified with immunocytochemistry and in situ hybridization. Eur J Neurosci 8: 621-628, 1996.
180. van Kerrebroeck P, Abrams P, Lange R, Slack M, Wyndaele JJ, Yalcin I, Bump RC. Duloxetine versus placebo in the treatment of European and Canadian women with stress urinary incontinence. BJOG 111: 249-257, 2004. (Pubitemid 38299590)
181. Vanderhorst VG, Holstege G. Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359: 457-475, 1995.
182. Vanderhorst VG, Holstege G. Nucleus retroambiguus projections to lumbosacral motoneuronal cell groups in the male cat. J Comp Neurol 382: 77-88, 1997.
183. Vanderhorst VG, Holstege G. Organization of lumbosacral motoneuronal cell groups innervating hindlimb, pelvic floor, and axial muscles in the cat. J Comp Neurol 382: 46-76, 1997.
184. Wallner C, Maas CP, Dabhoiwala NF, Lamers WH, DeRuiter MC. Innervation of the pelvic floor muscles: a reappraisal for the levator ani nerve. Obstet Gynecol 108: 529-534, 2006. (Pubitemid 44337092)
185. Wallner C, van Wissen J, Maas CP, Dabhoiwala NF, Deruiter MC, Lamers WH. The contribution of the levator ani nerve and the pudendal nerve to the innervation of the levator ani muscles; a study in human fetuses. Eur Urol 54: 1143-1144, 2007.
186. Wefer B, Reitz A, Knapp PA, Bannowsky A, Juenemann KP, Schurch B. Conditioning stimulus can influence an external urethral sphincter contraction evoked by a magnetic stimulation. Neurourol Urodyn 24: 311-317, 2005.
187. Weidner AC, Barber MD, Visco AG, Bump RC, Sanders DB. Pelvic muscle electromyography of levator ani and external anal sphincter in nulliparous women and women with pelvic floor dysfunction. Am J Obstet Gynecol 183: 1390-1399, 2000.
188. Weidner AC, Jamison MG, Branham V, South MM, Borawski KM, Romero AA. Neuropathic injury to the levator ani occurs in 1 in 4 primiparous women. Am J Obstet Gynecol 195: 1851-1856, 2006.
189. Weidner AC, Sanders DB, Nandedkar SD, Bump RC. Quantitative electromyographic analysis of levator ani and external anal sphincter muscles of nulliparous women. Am J Obstet Gynecol 183: 1249-1256, 2000.
190. Weidner AC, South MM, Sanders DB, Stinnett SS. Change in urethral sphincter neuromuscular function during pregnancy persists after delivery. Am J Obstet Gynecol 201: 529.e1-529.e6, 2009.
191. Wieslander CK, Roshanravan SM, Wai CY, Schaffer JI, Corton MM. Uterosacral ligament suspension sutures: Anatomic relationships in unembalmed female cadavers. Am J Obstet Gynecol 197: 672.e1-672.e6, 2007.
192. Wunderlich M, Swash M. The overlapping innervation of the two sides of the external anal sphincter by the pudendal nerves. J Neurol Sci 59: 97-109, 1983.
193. 5A receptors are expressed by different motoneuron populations in rat Onuf's nucleus. J Comp Neurol 502: 620-634, 2007.
194. Yoshiyama M, de Groat WC. Effect of bilateral hypogastric nerve transection on voiding dysfunction in rats with spinal cord injury. Exp Neurol 175: 191-197, 2002.
195. Yoshiyama M, Roppolo JR, de Groat WC. Alteration by urethane of glutamatergic control of micturition. Eur J Pharmacol 264: 417-425, 1994.
196. Yoshiyama M, Roppolo JR, de Groat WC. Effects of GYKI 52466 and CNQX, AMPA/kainate receptor antagonists, on the micturition reflex in the rat. Brain Res 691: 185-194, 1995.
197. Yoshiyama M, Roppolo JR, de Groat WC. Effects of LY215490, a competitive α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, on the micturition reflex in the rat. J Pharmacol Exp Ther 280: 894-904, 1997.
198. Yoshiyama M, Roppolo JR, de Groat WC. Effects of MK-801 on the micturition reflex in the rat-possible sites of action. J Pharmacol Exp Ther 265: 844-850, 1993.
199. Yoshiyama M, Roppolo JR, de Groat WC. Interactions between glutamatergic and monoaminergic systems controlling the micturition reflex in the urethane-anesthetized rat. Brain Res 639: 300-308, 1994.
200. Yoshiyama M, Roppolo JR, de Groat WC. Interactions between NMDA and AMPA/kainate receptors in the control of micturition in the rat. Eur J Pharmacol 287: 73-78, 1995.
201. Yoshiyama M, Roppolo JR, Rihmland J, Blastos B, deGroat WC. The effects of MK-801, an NMDA receptor antagonist, on the micturition reflex in the rat. Neurosci Lett 126: 141-144, 1991.
202. Yoshiyama M, Roppolo JR, Thor KB, de Groat WC. Effects of LY274614, a competitive NMDA receptor antagonist, on the micturition reflex in the urethane-anaesthetized rat. Br J Pharmacol 110: 77-86, 1993.
203. Zhang M, Moller M, Broman J, Sukiasyan N, Wienecke J, Hultborn H. Expression of calcium channel CaV1.3 in cat spinal cord: light and electron microscopic immunohistochemical study. J Comp Neurol 507: 1109-1127, 2008.
204. Zinner N, Scholfield D, Soma K, Darekar A, Grant L, Mills I. A phase 2, 8 week, multicenter, randomized, double blind, placebo controlled parallel group study evaluating the efficacy, tolerability, and safety of [S,S]-reboxetine (PNU-165442G) for stress urinary incontinence in women. J Urol 179: 569-570, 2008.