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Afferent Mechanism in the Urinary Tract

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Urinary Tract

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 2011))

Abstract

Much of the current research on lower urinary tract dysfunction is focused on afferent mechanisms. The main goals are to define and modulate the signaling pathways by which afferent information is generated and conveyed to the central nervous system. Alterations in bladder afferent mechanisms are a potential source of voiding dysfunction and an emerging source of drug targets. Even some established drug therapies such as muscarinic receptor antagonists, as well as emerging therapies such as botulinum toxin type-A, may act partly through afferent mechanisms. This review presents up-to-date findings on the localization of afferent fiber types within the bladder wall, afferent receptors and transmitters, and how these may communicate with the urothelium, interstitial cells, and detrusor smooth muscle to regulate micturition in normal and pathological bladders. Peripheral and central mechanisms of afferent sensitization and myogenic mechanisms that lead to detrusor overactivity, overactive bladder symptoms, and urgency sensations are also covered as well as new therapeutic approaches and new and established methods of measuring afferent activity.

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References

  • Abrams P, Andersson KE (2007) Muscarinic receptor antagonists for overactive bladder. BJU Int 100:987–1006

    CAS  PubMed  Google Scholar 

  • Andersson KE (2002) Bladder activation: afferent mechanisms. Urology 59:43–50

    PubMed  Google Scholar 

  • Andersson KE, Arner A (2004) Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 84:935–986

    CAS  PubMed  Google Scholar 

  • Andrews PV, Helme RD (1987) Neurogenic plasma extravasation in response to mechanical, chemical and thermal stimuli. Clin Exp Neurol 23:95–100

    CAS  PubMed  Google Scholar 

  • Apodaca G, Balestreire E, Birder LA (2007) The uroepithelial-associated sensory web. Kidney Int 72:1057–1064

    CAS  PubMed  Google Scholar 

  • Apostolidis A, Brady CM, Yiangou Y, Davis J, Fowler CJ, Anand P (2005a) Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 65:400–405

    PubMed  Google Scholar 

  • Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P (2005b) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174:977–982, discussion 82–83

    CAS  PubMed  Google Scholar 

  • Apostolidis A, Gonzales GE, Fowler CJ (2006) Effect of intravesical Resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation. Eur Urol 50:1299–1305

    CAS  PubMed  Google Scholar 

  • Araki I, de Groat WC (1997) Developmental synaptic depression underlying reorganization of visceral reflex pathways in the spinal cord. J Neurosci 17:8402–8407

    CAS  PubMed  Google Scholar 

  • Araki I, Du S, Kobayashi H, Sawada N, Mochizuki T, Zakoji H, Takeda M (2008) Roles of mechanosensitive ion channels in bladder sensory transduction and overactive bladder. Int J Urol 15:681–687

    PubMed  Google Scholar 

  • Avelino A, Cruz C, Nagy I, Cruz F (2002) Vanilloid receptor 1 expression in the rat urinary tract. Neuroscience 109:787–798

    CAS  PubMed  Google Scholar 

  • Bielefeldt K, Lamb K, Gebhart GF (2006) Convergence of sensory pathways in the development of somatic and visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 291:G658–G665

    CAS  PubMed  Google Scholar 

  • Biers SM, Reynard JM, Doore T, Brading AF (2006) The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor. BJU Int 97:612–616

    CAS  PubMed  Google Scholar 

  • Birder LA, Roppolo JR, Erickson VL, de Groat WC (1999) Increased c-fos expression in spinal lumbosacral projection neurons and preganglionic neurons after irritation of the lower urinary tract in the rat. Brain Res 834:55–65

    CAS  PubMed  Google Scholar 

  • Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina MJ (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860

    CAS  PubMed  Google Scholar 

  • Brading AF (1997) A myogenic basis for the overactive bladder. Urology 50:57–67, discussion 68–73

    CAS  PubMed  Google Scholar 

  • Brading AF (2006) Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. J Physiol 570:13–22

    CAS  PubMed  Google Scholar 

  • Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P (2004) Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int 93:770–776

    CAS  PubMed  Google Scholar 

  • Brookes SJ, Chen BN, Costa M, Humphreys CM (1999) Initiation of peristalsis by circumferential stretch of flat sheets of guinea-pig ileum. J Physiol 516(Pt 2):525–538

    CAS  PubMed  Google Scholar 

  • Burgard EC, Fraser MO, Thor KB (2003) Serotonergic modulation of bladder afferent pathways. Urology 62:10–15

    PubMed  Google Scholar 

  • Callsen-Cencic P, Mense S (1997) Expression of neuropeptides and nitric oxide synthase in neurones innervating the inflamed rat urinary bladder. J Auton Nerv Syst 65:33–44

    CAS  PubMed  Google Scholar 

  • Carlton SM, Coggeshall RE (1999) Inflammation-induced changes in peripheral glutamate receptor populations. Brain Res 820:63–70

    CAS  PubMed  Google Scholar 

  • Cefalu JS, Guillon MA, Burbach LR, Zhu QM, Hu DQ, Ho MJ, Ford AP, Nunn PA, Cockayne DA (2009) Selective pharmacological blockade of the TRPV1 receptor suppresses sensory reflexes of the rodent bladder. J Urol 182:776–785

    CAS  PubMed  Google Scholar 

  • Charrua A, Reguenga C, Paule CC, Nagy I, Cruz F, Avelino A (2008) Cystitis is associated with TRPV1b-downregulation in rat dorsal root ganglia. Neuroreport 19:1469–1472

    CAS  PubMed  Google Scholar 

  • Cheng CL, de Groat WC (2004) 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

    CAS  PubMed  Google Scholar 

  • Chopra B, Gever J, Barrick SR, Hanna-Mitchell AT, Beckel JM, Ford AP, Birder LA (2008) Expression and function of rat urothelial P2Y receptors. Am J Physiol Renal Physiol 294:F821–F829

    CAS  PubMed  Google Scholar 

  • Christianson JA, Liang R, Ustinova EE, Davis BM, Fraser MO, Pezzone MA (2007) Convergence of bladder and colon sensory innervation occurs at the primary afferent level. Pain 128:235–243

    PubMed  Google Scholar 

  • Chuang YC, Yoshimura N, Huang CC, Chiang PH, Chancellor MB (2004) Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats. J Urol 172:1529–1532

    CAS  PubMed  Google Scholar 

  • Chuang YC, Tyagi P, Huang CC, Yoshimura N, Wu M, Kaufman J, Chancellor MB (2009) Urodynamic and immunohistochemical evaluation of intravesical botulinum toxin A delivery using liposomes. J Urol 182:786–792

    CAS  PubMed  Google Scholar 

  • Cockayne DA, Dunn PM, Zhong Y, Rong W, Hamilton SG, Knight GE, Ruan H-Z, Ma B, Yip P, Nunn P, McMahon SB, Burnstock G, Ford APDW (2005) P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2 receptor subunit in mediating multiple sensory effects of ATP. J Physiol 567:621–639

    CAS  PubMed  Google Scholar 

  • Coggeshall RE (1980) Law of separation of function of the spinal roots. Physiol Rev 60:716–755

    CAS  PubMed  Google Scholar 

  • Coggeshall RE, Carlton SM (1998) Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and myelinated axons in the periphery. J Comp Neurol 391:78–86

    CAS  PubMed  Google Scholar 

  • Coggeshall RE, Coulter JD, Willis WD Jr (1974) Unmyelinated axons in the ventral roots of the cat lumbosacral enlargement. J Comp Neurol 153:39–58

    CAS  PubMed  Google Scholar 

  • Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D (2007) Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 583:663–674

    CAS  PubMed  Google Scholar 

  • Dang K, Lamb K, Cohen M, Bielefeldt K, Gebhart GF (2008) Cyclophosphamide-induced bladder inflammation sensitizes and enhances P2X receptor function in rat bladder sensory neurons. J Neurophysiol 99:49–59

    CAS  PubMed  Google Scholar 

  • Darblade B, Behr-Roussel D, Gorny D, Lebret T, Benoit G, Hieble JP, Brooks D, Alexandre L, Giuliano F (2005) Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle. World J Urol 23:147–151

    CAS  PubMed  Google Scholar 

  • Dattilio A, Vizzard MA (2005) Up-regulation of protease activated receptors in bladder after cyclophosphamide induced cystitis and colocalization with capsaicin receptor (VR1) in bladder nerve fibers. J Urol 173:635–639

    CAS  PubMed  Google Scholar 

  • Dawson NJ, Schmid H, Pierau FK (1992) Pre-spinal convergence between thoracic and visceral nerves of the rat. Neurosci Lett 138:149–152

    CAS  PubMed  Google Scholar 

  • De Groat WC (1986) Spinal cord projections and neuropeptides in visceral afferent neurons. Prog Brain Res 67:165–187

    PubMed  Google Scholar 

  • de Groat WC (1997) A neurologic basis for the overactive bladder. Urology 50:36–52, discussion 53–6

    PubMed  Google Scholar 

  • De Groat WC, Lalley PM (1972) Reflex firing in the lumbar sympathetic outflow to activation of vesical afferent fibres. J Physiol 226:289–309

    PubMed  Google Scholar 

  • de Groat WC, Ryall RW (1969) Reflexes to sacral parasympathetic neurones concerned with micturition in the cat. J Physiol 200:87–108

    PubMed  Google Scholar 

  • De Wachter S, Wyndaele JJ (2003) Intravesical oxybutynin: a local anesthetic effect on bladder C afferents. J Urol 169:1892–1895

    PubMed  Google Scholar 

  • Dmitrieva N, Johnson OL, Berkley KJ (2001) Bladder inflammation and hypogastric neurectomy influence uterine motility in the rat. Neurosci Lett 313:49–52

    CAS  PubMed  Google Scholar 

  • Du S, Araki I, Yoshiyama M, Nomura T, Takeda M (2007) Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology 70:826–831

    PubMed  Google Scholar 

  • Duong M, Downie JW, Du HJ (1999) Transmission of afferent information from urinary bladder, urethra and perineum to periaqueductal gray of cat. Brain Res 819:108–119

    CAS  PubMed  Google Scholar 

  • Ferguson DR, Kennedy I, Burton TJ (1997) ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes – a possible sensory mechanism? J Physiol 505(Pt 2):503–511

    CAS  PubMed  Google Scholar 

  • Fitzpatrick CC, DeLancey JO, Elkins TE, McGuire EJ (1993) Vulvar vestibulitis and interstitial cystitis: a disorder of urogenital sinus-derived epithelium? Obstet Gynecol 81:860–862

    CAS  PubMed  Google Scholar 

  • Fowler CJ, Griffiths D, de Groat WC (2008) The neural control of micturition. Nat Rev Neurosci 9:453–466

    CAS  PubMed  Google Scholar 

  • Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I, Van Leuven F, Voets T, De Ridder D, Nilius B (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462

    CAS  PubMed  Google Scholar 

  • Gillespie JI (2004) The autonomous bladder: a view of the origin of bladder overactivity and sensory urge. BJU Int 93:478–483

    CAS  PubMed  Google Scholar 

  • Gillespie JI, van Koeveringe GA, de Wachter SG, de Vente J (2009) On the origins of the sensory output from the bladder: the concept of afferent noise. BJU Int 103:1324–1333

    PubMed  Google Scholar 

  • Griffiths DJ, Tadic SD, Schaefer W, Resnick NM (2009) Cerebral control of the lower urinary tract: How age-related changes might predispose to urge incontinence. Neuroimage 47(3):981–986

    PubMed  Google Scholar 

  • Grol S, Essers PB, van Koeveringe GA, Martinez-Martinez P, de Vente J, Gillespie JI (2009) M(3) muscarinic receptor expression on suburothelial interstitial cells. BJU Int 104:398–405

    CAS  PubMed  Google Scholar 

  • Guerios SD, Wang ZY, Bjorling DE (2006) Nerve growth factor mediates peripheral mechanical hypersensitivity that accompanies experimental cystitis in mice. Neurosci Lett 392:193–197

    CAS  PubMed  Google Scholar 

  • Habler HJ, Janig W, Koltzenburg M (1990) Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat. J Physiol 425:545–562

    CAS  PubMed  Google Scholar 

  • Habler HJ, Janig W, Koltzenburg M (1993a) Myelinated primary afferents of the sacral spinal cord responding to slow filling and distension of the cat urinary bladder. J Physiol 463:449–460

    CAS  PubMed  Google Scholar 

  • Habler HJ, Janig W, Koltzenburg M (1993b) Receptive properties of myelinated primary afferents innervating the inflamed urinary bladder of the cat. J Neurophysiol 69:395–405

    CAS  PubMed  Google Scholar 

  • Haga N, Aikawa K, Shishido K, Takahashi N, Yanagida T, Yamaguchi O (2009) Effect of long-term oxybutynin administration on c-Fos expression in spinal neurons: inhibition of antimuscarinics on bladder afferents in conscious rats. Urology 73:200–204

    PubMed  Google Scholar 

  • Hirayama A, Fujimoto K, Matsumoto Y, Ozono S, Hirao Y (2003) Positive response to ice water test associated with high-grade bladder outlet obstruction in patients with benign prostatic hyperplasia. Urology 62:909–913

    PubMed  Google Scholar 

  • Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143–201

    CAS  PubMed  Google Scholar 

  • Hou S, Duale H, Rabchevsky AG (2009) Intraspinal sprouting of unmyelinated pelvic afferents after complete spinal cord injury is correlated with autonomic dysreflexia induced by visceral pain. Neuroscience 159:369–379

    CAS  PubMed  Google Scholar 

  • Iijima K, De Wachter S, Wyndaele JJ (2007) Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve. Eur Urol 52:842–847

    PubMed  Google Scholar 

  • Ito K, Iwami A, Katsura H, Ikeda M (2008) Therapeutic effects of the putative P2X3/P2X2/3 antagonist A-317491 on cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol 377:483–490

    CAS  PubMed  Google Scholar 

  • Janig W, Morrison JF (1986) Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception. Prog Brain Res 67:87–114

    CAS  PubMed  Google Scholar 

  • Jiang CH, Mazieres L, Lindstrom S (2009) Gating of the micturition reflex by tonic activation of bladder cold receptors in the cat. Neurourol Urodyn 28(6):555–560

    CAS  PubMed  Google Scholar 

  • Kamo I, Chancellor MB, de Groat WC, Yoshimura N (2005) Differential effects of activation of peripheral and spinal tachykinin neurokinin(3) receptors on the micturition reflex in rats. J Urol 174:776–781

    CAS  PubMed  Google Scholar 

  • Keast JR, Stephensen TM (2000) Glutamate and aspartate immunoreactivity in dorsal root ganglion cells supplying visceral and somatic targets and evidence for peripheral axonal transport. J Comp Neurol 424:577–587

    CAS  PubMed  Google Scholar 

  • Kinder RB, Mundy AR (1987) Pathophysiology of idiopathic detrusor instability and detrusor hyper-reflexia. An in vitro study of human detrusor muscle. Br J Urol 60:509–515

    CAS  PubMed  Google Scholar 

  • King AE, Lopez-Garcia JA (1993) Excitatory amino acid receptor-mediated neurotransmission from cutaneous afferents in rat dorsal horn in vitro. J Physiol 472:443–457

    CAS  PubMed  Google Scholar 

  • Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, Tokunaga A, Noguchi K (2005) Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors. J Comp Neurol 493:596–606

    CAS  PubMed  Google Scholar 

  • Kubota Y, Biers SM, Kohri K, Brading AF (2006) Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder. Neurourol Urodyn 25:205–210

    CAS  PubMed  Google Scholar 

  • Kullmann FA, Artim DE, Birder LA, de Groat WC (2008) Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity. J Neurosci 28:1977–1987

    CAS  PubMed  Google Scholar 

  • Laird JM, Olivar T, Roza C, De Felipe C, Hunt SP, Cervero F (2000) Deficits in visceral pain and hyperalgesia of mice with a disruption of the tachykinin NK1 receptor gene. Neuroscience 98:345–352

    CAS  PubMed  Google Scholar 

  • Lamb K, Gebhart GF, Bielefeldt K (2004) Increased nerve growth factor expression triggers bladder overactivity. J Pain 5:150–156

    CAS  PubMed  Google Scholar 

  • Lazzeri M, Beneforti P, Benaim G, Maggi CA, Lecci A, Turini D (1996) Intravesical capsaicin for treatment of severe bladder pain: a randomized placebo controlled study. J Urol 156:947–952

    CAS  PubMed  Google Scholar 

  • le Feber J, van Asselt E, van Mastrigt R (2004) Afferent bladder nerve activity in the rat: a mechanism for starting and stopping voiding contractions. Urol Res 32:395–405

    PubMed  Google Scholar 

  • Lecci A, Tramontana M, Giuliani S, Criscuoli M, Maggi CA (1998) Effect of tachykinin NK2 receptor blockade on detrusor hyperreflexia induced by bacterial toxin in rats. J Urol 160:206–209

    CAS  PubMed  Google Scholar 

  • Liu HT, Kuo HC (2008) Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment. Urology 72:104–108, discussion 08

    PubMed  Google Scholar 

  • Liu HT, Chancellor MB, Kuo HC (2008) Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol 56(4):700–706

    Google Scholar 

  • Liu HT, Tyagi P, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int 104(10):1476–1481

    CAS  PubMed  Google Scholar 

  • Maggi CA (1995) Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol 45:1–98

    CAS  PubMed  Google Scholar 

  • Malykhina AP (2007) Neural mechanisms of pelvic organ cross-sensitization. Neuroscience 149:660–672

    CAS  PubMed  Google Scholar 

  • Malykhina AP, Qin C, Foreman RD, Akbarali HI (2004) Colonic inflammation increases Na + currents in bladder sensory neurons. Neuroreport 15:2601–2605

    CAS  PubMed  Google Scholar 

  • Malykhina AP, Qin C, Greenwood-van Meerveld B, Foreman RD, Lupu F, Akbarali HI (2006) Hyperexcitability of convergent colon and bladder dorsal root ganglion neurons after colonic inflammation: mechanism for pelvic organ cross-talk. Neurogastroenterol Motil 18:936–948

    CAS  PubMed  Google Scholar 

  • Mariappan P, Alhasso A, Ballantyne Z, Grant A, N’Dow J (2007) Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence: a systematic review. Eur Urol 51(1):67–74

    CAS  PubMed  Google Scholar 

  • Masuda H, Chancellor MB, Kihara K, Sakai Y, Koga F, Azuma H, de Groat WC, Yoshimura N (2009a) Effects of cholinesterase inhibition in supraspinal and spinal neural pathways on the micturition reflex in rats. BJU Int 104(8):1163–1169

    CAS  PubMed  Google Scholar 

  • Masuda H, Ichiyanagi N, Yokoyama M, Sakai Y, Kihara K, Chancellor MB, de Groat WC, Yoshimura N (2009b) Muscarinic receptor activation in the lumbosacral spinal cord ameliorates bladder irritation in rat cystitis models. BJU Int 104(10):1531–1537

    CAS  PubMed  Google Scholar 

  • McCarthy CJ, Zabbarova IV, Brumovsky PR, Roppolo JR, Gebhart GF, Kanai AJ (2009) Spontaneous contractions evoke afferent nerve firing in mouse bladders with detrusor overactivity. J Urol 181:1459–1466

    PubMed  Google Scholar 

  • Messori E, Rizzi CA, Candura SM, Lucchelli A, Balestra B, Tonini M (1995) 5-Hydroxytryptamine receptors that facilitate excitatory neuromuscular transmission in the guinea-pig isolated detrusor muscle. Br J Pharmacol 115:677–683

    CAS  PubMed  Google Scholar 

  • Michaelis M, Habler HJ, Jaenig W (1996) Silent afferents: a separate class of primary afferents? Clin Exp Pharmacol Physiol 23:99–105

    CAS  PubMed  Google Scholar 

  • Mills IW, Greenland JE, McMurray G, McCoy R, Ho KM, Noble JG, Brading AF (2000) Studies of the pathophysiology of idiopathic detrusor instability: the physiological properties of the detrusor smooth muscle and its pattern of innervation. J Urol 163:646–651

    CAS  PubMed  Google Scholar 

  • Moldwin RM (2002) Similarities between interstitial cystitis and male chronic pelvic pain syndrome. Curr Urol Rep 3:313–318

    PubMed  Google Scholar 

  • Morgan C, Nadelhaft I, de Groat WC (1981) The distribution of visceral primary afferents from the pelvic nerve to Lissauer’s tract and the spinal gray matter and its relationship to the sacral parasympathetic nucleus. J Comp Neurol 201:415–440

    CAS  PubMed  Google Scholar 

  • Morrison J (1999) The activation of bladder wall afferent nerves. Exp Physiol 84:131–136

    CAS  PubMed  Google Scholar 

  • Morrison J, Wen J, Kibble A (1999) Activation of pelvic afferent nerves from the rat bladder during filling. Scand J Urol Nephrol Suppl 201:73–75

    CAS  PubMed  Google Scholar 

  • Morrison TC, Dmitrieva N, Winnard KP, Berkley KJ (2006) Opposing viscerovisceral effects of surgically induced endometriosis and a control abdominal surgery on the rat bladder. Fertil Steril 86:1067–1073

    PubMed  Google Scholar 

  • Namasivayam S, Eardley I, Morrison JF (1998) A novel in vitro bladder pelvic nerve afferent model in the rat. Br J Urol 82:902–905

    CAS  PubMed  Google Scholar 

  • Namasivayam S, Eardley I, Morrison JF (1999) Purinergic sensory neurotransmission in the urinary bladder: an in vitro study in the rat. BJU Int 84:854–860

    CAS  PubMed  Google Scholar 

  • Nilsson Remahl AI, Masterman T, Risling M (2008) Re-utilization of Schwann cells during ingrowth of ventral root afferents in perinatal kittens. J Anat 213:194–201

    PubMed  Google Scholar 

  • Oddiah D, Anand P, McMahon SB, Rattray M (1998) Rapid increase of NGF, BDNF and NT-3 mRNAs in inflamed bladder. Neuroreport 9:1455–1458

    CAS  PubMed  Google Scholar 

  • Otsuka A, Shinbo H, Matsumoto R, Kurita Y, Ozono S (2008) Expression and functional role of beta-adrenoceptors in the human urinary bladder urothelium. Naunyn Schmiedebergs Arch Pharmacol 377:473–481

    CAS  PubMed  Google Scholar 

  • Payne CK, Mosbaugh PG, Forrest JB, Evans RJ, Whitmore KE, Antoci JP, Perez-Marrero R, Jacoby K, Diokno AC, O'Reilly KJ, Griebling TL, Vasavada SP, Yu AS, Frumkin LR (2005) Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol 173:1590–1594

    CAS  PubMed  Google Scholar 

  • Pezzone MA, Liang R, Fraser MO (2005) A model of neural cross-talk and irritation in the pelvis: implications for the overlap of chronic pelvic pain disorders. Gastroenterology 128:1953–1964

    PubMed  Google Scholar 

  • Pontari MA, Ruggieri MR (2008) Mechanisms in prostatitis/chronic pelvic pain syndrome. J Urol 179:S61–S67

    PubMed  Google Scholar 

  • Qin C, Foreman RD (2004) Viscerovisceral convergence of urinary bladder and colorectal inputs to lumbosacral spinal neurons in rats. Neuroreport 15:467–471

    PubMed  Google Scholar 

  • Qin C, Malykhina AP, Akbarali HI, Foreman RD (2005) Cross-organ sensitization of lumbosacral spinal neurons receiving urinary bladder input in rats with inflamed colon. Gastroenterology 129:1967–1978

    PubMed  Google Scholar 

  • Risling M, Dalsgaard CJ, Cukierman A, Cuello AC (1984) Electron microscopic and immunohistochemical evidence that unmyelinated ventral root axons make u-turns or enter the spinal pia mater. J Comp Neurol 225:53–63

    CAS  PubMed  Google Scholar 

  • Ritter AM, Martin WJ, Thorneloe KS (2009) The voltage-gated sodium channel Nav1.9 is required for inflammation-based urinary bladder dysfunction. Neurosci Lett 452:28–32

    CAS  PubMed  Google Scholar 

  • Rong W, Spyer KM, Burnstock G (2002) Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J Physiol 541:591–600

    CAS  PubMed  Google Scholar 

  • Rouzade-Dominguez ML, Pernar L, Beck S, Valentino RJ (2003) Convergent responses of Barrington’s nucleus neurons to pelvic visceral stimuli in the rat: a juxtacellular labelling study. Eur J Neurosci 18:3325–3334

    PubMed  Google Scholar 

  • Ruan HZ, Burnstock G (2003) Localisation of P2Y1 and P2Y4 receptors in dorsal root, nodose and trigeminal ganglia of the rat. Histochem Cell Biol 120:415–426

    CAS  PubMed  Google Scholar 

  • Ruan HZ, Birder LA, de Groat WC, Tai C, Roppolo J, Buffington CA, Burnstock G (2005) Localization of P2X and P2Y receptors in dorsal root ganglia of the cat. J Histochem Cytochem 53:1273–1282

    CAS  PubMed  Google Scholar 

  • Saban MR, Nguyen NB, Hammond TG, Saban R (2002) Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. Am J Pathol 160:2095–2110

    CAS  PubMed  Google Scholar 

  • Sculptoreanu A, Yoshimura N, de Groat WC (2004) KW-7158 [(2 S)-(+)-3, 3, 3-trifluoro-2-hydroxy-2-methyl-N-(5, 5, 10-trioxo-4, 10-dihydro thieno[3, 2-c][1]benzothiepin-9-yl)propanamide] enhances A-type K + currents in neurons of the dorsal root ganglion of the adult rat. J Pharmacol Exp Ther 310:159–168

    CAS  PubMed  Google Scholar 

  • Sellers DJ, Chess-Williams R, Chapple CR (2000) 5-Hydroxytryptamine-induced potentiation of cholinergic responses to electrical field stimulation in pig detrusor muscle. BJU Int 86:714–718

    CAS  PubMed  Google Scholar 

  • Sengupta JN, Gebhart GF (1994a) Characterization of mechanosensitive pelvic nerve afferent fibers innervating the colon of the rat. J Neurophysiol 71:2046–2060

    CAS  PubMed  Google Scholar 

  • Sengupta JN, Gebhart GF (1994b) Mechanosensitive properties of pelvic nerve afferent fibers innervating the urinary bladder of the rat. J Neurophysiol 72:2420–2430

    CAS  PubMed  Google Scholar 

  • Shea VK, Cai R, Crepps B, Mason JL, Perl ER (2000) Sensory fibers of the pelvic nerve innervating the Rat’s urinary bladder. J Neurophysiol 84:1924–1933

    CAS  PubMed  Google Scholar 

  • Shimizu N, Nakahara T, Saito M, Ishii K (2007) Role of capsaicin-sensitive sensory nerves in protease-activated receptor-2-mediated contraction of rat urinary bladder. Eur J Pharmacol 569:145–148

    CAS  PubMed  Google Scholar 

  • Silva C, Ribeiro MJ, Cruz F (2002) The effect of intravesical resiniferatoxin in patients with idiopathic detrusor instability suggests that involuntary detrusor contractions are triggered by C-fiber input. J Urol 168:575–579

    CAS  PubMed  Google Scholar 

  • Silva C, Silva J, Ribeiro MJ, Avelino A, Cruz F (2005) Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial. Eur Urol 48:650–655

    CAS  PubMed  Google Scholar 

  • Steers WD, Ciambotti J, Etzel B, Erdman S, de Groat WC (1991) Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol 310:401–410

    CAS  PubMed  Google Scholar 

  • Steers WD, Mackway-Gerardi AM, Ciambotti J, de Groat WC (1994) Alterations in neural pathways to the urinary bladder of the rat in response to streptozotocin-induced diabetes. J Auton Nerv Syst 47:83–94

    CAS  PubMed  Google Scholar 

  • Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Hogestatt ED, Zygmunt PM (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399

    CAS  PubMed  Google Scholar 

  • Su X, Lashinger ES, Leon LA, Hoffman BE, Hieble JP, Gardner SD, Fries HE, Edwards RM, Li J, Laping NJ (2008a) An excitatory role for peripheral EP3 receptors in bladder afferent function. Am J Physiol Renal Physiol 295:F585–F594

    CAS  PubMed  Google Scholar 

  • Su X, Leon LA, Wu CW, Morrow DM, Jaworski JP, Hieble JP, Lashinger ES, Jin J, Edwards RM, Laping NJ (2008b) Modulation of bladder function by prostaglandin EP3 receptors in the central nervous system. Am J Physiol Renal Physiol 295:F984–F994

    CAS  PubMed  Google Scholar 

  • Sui GP, Wu C, Fry CH (2006) Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts. BJU Int 97:1327–1331

    CAS  PubMed  Google Scholar 

  • Tai C, Smerin SE, de Groat WC, Roppolo JR (2006) Pudendal-to-bladder reflex in chronic spinal-cord-injured cats. Exp Neurol 197:225–234

    PubMed  Google Scholar 

  • Talaat M (1937) Afferent impulses in the nerves supplying the urinary bladder. J Physiol 89:1–13

    CAS  PubMed  Google Scholar 

  • Thor KB, Morgan C, Nadelhaft I, Houston M, De Groat WC (1989) Organization of afferent and efferent pathways in the pudendal nerve of the female cat. J Comp Neurol 288:263–279

    CAS  PubMed  Google Scholar 

  • Thor KB, Katofiasc MA, Danuser H, Springer J, Schaus JM (2002) The role of 5-HT(1A) receptors in control of lower urinary tract function in cats. Brain Res 946:290–297

    CAS  PubMed  Google Scholar 

  • Tucci P, Bartocci C, Bolle P (2002) Cyclo-oxygenase- and capsaicin-sensitive afferent fibres affect Beta-adrenoceptor-evoked response in the rat urinary bladder. Pharmacology 64:57–62

    CAS  PubMed  Google Scholar 

  • Ustinova EE, Fraser MO, Pezzone MA (2006) Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization. Am J Physiol Renal Physiol 290:F1478–F1487

    CAS  PubMed  Google Scholar 

  • Ustinova EE, Gutkin DW, Pezzone MA (2007) Sensitization of pelvic nerve afferents and mast cell infiltration in the urinary bladder following chronic colonic irritation is mediated by neuropeptides. Am J Physiol Renal Physiol 292:F123–F130

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1995a) Increased expression of neuronal nitric oxide synthase (NOS) in visceral neurons after nerve injury. J Neurosci 15:4033–4045

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1995b) Increased expression of neuronal nitric oxide synthase in dorsal root ganglion neurons after systemic capsaicin administration. Neuroscience 67:1–5

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1996) Increased expression of neuronal nitric oxide synthase in bladder afferent pathways following chronic bladder irritation. J Comp Neurol 370:191–202

    CAS  PubMed  Google Scholar 

  • Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 21:5670–5677

    CAS  PubMed  Google Scholar 

  • Walczak JS, Price TJ, Cervero F (2009) Cannabinoid CB1 receptors are expressed in the mouse urinary bladder and their activation modulates afferent bladder activity. Neuroscience 159:1154–1163

    CAS  PubMed  Google Scholar 

  • Wang ZY, Wang P, Merriam FV, Bjorling DE (2008) Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. Pain 139:158–167

    CAS  PubMed  Google Scholar 

  • Watanabe T, Yokoyama T, Sasaki K, Nozaki K, Ozawa H, Kumon H (2004) Intravesical resiniferatoxin for patients with neurogenic detrusor overactivity. Int J Urol 11:200–205

    CAS  PubMed  Google Scholar 

  • Weaver LC (1985) Organization of sympathetic responses to distension of urinary bladder. Am J Physiol Regul Integr Comp Physiol 248:R236–R240

    CAS  Google Scholar 

  • Wesselmann U (2001) Neurogenic inflammation and chronic pelvic pain. World J Urol 19:180–185

    CAS  PubMed  Google Scholar 

  • Westlund KN, Sun YC, Sluka KA, Dougherty PM, Sorkin LS, Willis WD (1992) Neural changes in acute arthritis in monkeys. II. Increased glutamate immunoreactivity in the medial articular nerve. Brain Res Brain Res Rev 17:15–27

    CAS  PubMed  Google Scholar 

  • Winnard KP, Dmitrieva N, Berkley KJ (2006) Cross-organ interactions between reproductive, gastrointestinal, and urinary tracts: modulation by estrous stage and involvement of the hypogastric nerve. Am J Physiol Regul Integr Comp Physiol 291:R1592–R1601

    CAS  PubMed  Google Scholar 

  • Wiseman OJ, Fowler CJ, Landon DN (2003) The role of the human bladder lamina propria myofibroblast. BJU Int 91:89–93

    CAS  PubMed  Google Scholar 

  • Xu L, Gebhart GF (2008) Characterization of mouse lumbar splanchnic and pelvic nerve urinary bladder mechanosensory afferents. J Neurophysiol 99:244–253

    PubMed  Google Scholar 

  • Yamanishi T, Chapple CR, Yasuda K, Yoshida K, Chess-Williams R (2002) The role of beta(3)-adrenoceptors in mediating relaxation of porcine detrusor muscle. Br J Pharmacol 135:129–134

    CAS  PubMed  Google Scholar 

  • Yamanishi T, Yasuda K, Kitahara S, Nakai H, Yoshida K, Iizuka H (2006) Effects of 138-355, a beta3-adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro. Neurourol Urodyn 25:815–819

    CAS  PubMed  Google Scholar 

  • Yokoyama O, Yusup A, Miwa Y, Oyama N, Aoki Y, Akino H (2005) Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats. J Urol 174:2032–2036

    CAS  PubMed  Google Scholar 

  • Yokoyama T, Kumon H, Nagai A (2008) Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder. Neurourol Urodyn 27:417–420

    PubMed  Google Scholar 

  • Yoshimura N, de Groat WC (1999) Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation. J Neurosci 19:4644–4653

    CAS  PubMed  Google Scholar 

  • Yoshimura M, Jessell T (1990) Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord. J Physiol 430:315–335

    CAS  PubMed  Google Scholar 

  • Yoshimura N, White G, Weight FF, de Groat WC (1994) Patch-clamp recordings from subpopulations of autonomic and afferent neurons identified by axonal tracing techniques. J Auton Nerv Syst 49:85–92

    CAS  PubMed  Google Scholar 

  • Yoshimura N, Seki S, de Groat WC (2001) Nitric oxide modulates Ca(2+) channels in dorsal root ganglion neurons innervating rat urinary bladder. J Neurophysiol 86:304–311

    CAS  PubMed  Google Scholar 

  • Yoshimura N, Seki S, Erickson KA, Erickson VL, Hancellor MB, de Groat WC (2003) Histological and electrical properties of rat dorsal root ganglion neurons innervating the lower urinary tract. J Neurosci 23:4355–4361

    CAS  PubMed  Google Scholar 

  • Yoshimura N, Kaiho Y, Miyazato M, Yunoki T, Tai C, Chancellor MB, Tyagi P (2008) Therapeutic receptor targets for lower urinary tract dysfunction. Naunyn Schmiedebergs Arch Pharmacol 377:437–448

    CAS  PubMed  Google Scholar 

  • Yu Y, de Groat WC (2008) Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder-pelvic nerve preparation by purinergic agonists and cyclophosphamide pretreatment. Am J Physiol Renal Physiol 294:F1146–F1156

    CAS  PubMed  Google Scholar 

  • Yu YF, Nichol MB, Yu AP, Ahn J (2005) Persistence and adherence of medications for chronic overactive bladder/urinary incontinence in the california medicaid program. Value Health 8:495–505

    PubMed  Google Scholar 

  • Zabbarova I, Birder L, Roppolo J, de Groat W, Kanai A (2009) Bladder-colon cross-sensitization induced bladder overactivity. Neurourol Urodyn 28:914–915

    Google Scholar 

  • Zagorodnyuk VP, Brookes SJ (2000) Transduction sites of vagal mechanoreceptors in the guinea pig esophagus. J Neurosci 20:6249–6255

    CAS  PubMed  Google Scholar 

  • Zagorodnyuk VP, Costa M, Brookes SJ (2006) Major classes of sensory neurons to the urinary bladder. Auton Neurosci 126–127:390–397

    PubMed  Google Scholar 

  • Zagorodnyuk VP, Gibbins IL, Costa M, Brookes SJ, Gregory SJ (2007) Properties of the major classes of mechanoreceptors in the guinea pig bladder. J Physiol 585:147–163

    CAS  PubMed  Google Scholar 

  • Zarghooni S, Wunsch J, Bodenbenner M, Bruggmann D, Grando SA, Schwantes U, Wess J, Kummer W, Lips KS (2007) Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. Life Sci 80:2308–2313

    CAS  PubMed  Google Scholar 

  • Zhou S, Bonasera L, Carlton SM (1996) Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport 7:895–900

    CAS  PubMed  Google Scholar 

  • Zinck ND, Rafuse VF, Downie JW (2007) Sprouting of CGRP primary afferents in lumbosacral spinal cord precedes emergence of bladder activity after spinal injury. Exp Neurol 204:777–790

    CAS  PubMed  Google Scholar 

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  1. University of Pittsburgh, School of Medicine, 3550 Terrace Street, A1224 Scaife Hall, Pittsburgh, PA, 15261, USA

    Anthony J. Kanai

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  1. Wake Forest University, Medical Center Blvd., Winston-Salem, 27157-1088, North Carolina, USA

    Karl-Erik Andersson

  2. Academic Medical Center, Dept. Pharmacology & Pharmacotherapy, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, Netherlands

    Martin C. Michel

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Kanai, A.J. (2011). Afferent Mechanism in the Urinary Tract. In: Andersson, KE., Michel, M. (eds) Urinary Tract. Handbook of Experimental Pharmacology, vol 2011. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16499-6_9

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