Skip to main content

Afferent Nerve Regulation of Bladder Function in Health and Disease

  • Chapter
  • First Online:
Sensory Nerves

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 194))

Abstract

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andrade EL, Ferreira J, Andre E, Calixto JB (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114

    PubMed  CAS  Google Scholar 

  • Apostolidis A, Fowler CJ (2008) The use of botulinum neurotoxin type A (BoNTA) in urology. J Neural Transm 115:593–605

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Apostolidis A, Dasgupta P, Fowler CJ (2006) Proposed mechanism for the efficacy of injected botulinum toxin in the treatment of human detrusor overactivity. Eur Urol 49:644–650

    PubMed  CAS  Google Scholar 

  • Apostolidis A, Jacques TS, Freeman A, Kalsi V, Popat R, Gonzales G, Datta SN, Ghazi-Noori S, Elneil S, Dasgupta P, Fowler CJ (2008) Histological changes in the urothelium and suburothelium of human overactive bladder following intradetrusor injections of botulinum neurotoxin type A for the treatment of neurogenic or idiopathic detrusor overactivity. Eur Urol 53:1245–1253

    PubMed  CAS  Google Scholar 

  • Applebaum AE, Vance WH, Coggeshall RE (1980) Segmental localization of sensory cells that innervate the bladder. J Comp Neurol 192:203–209

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Averill S, McMahon SB, Clary DO, Reichardt LF, Priestley JV (1995) Immunocytochemical localization of trkA receptors in chemically identified subgroups of adult rat sensory neurons. Eur J Neurosci 7:1484–1494

    PubMed  CAS  Google Scholar 

  • Bahns E, Ernsberger U, Janig W, Nelke A (1986) Functional characteristics of lumbar visceral afferent fibres from the urinary bladder and the urethra in the cat. Pflugers Arch 407:510–518

    PubMed  CAS  Google Scholar 

  • Bahns E, Halsband U, Janig W (1987) Responses of sacral visceral afferents from the lower urinary tract, colon and anus to mechanical stimulation. Pflugers Arch 410:296–303

    PubMed  CAS  Google Scholar 

  • Beckel JM, Kanai A, Lee SJ, de Groat WC, Birder LA (2006) Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells. Am J Physiol Renal Physiol 290:F103–F110

    PubMed  CAS  Google Scholar 

  • Bennett DL, Dmietrieva N, Priestley JV, Clary D, McMahon SB (1996) trkA, CGRP and IB4 expression in retrogradely labelled cutaneous and visceral primary sensory neurones in the rat. Neurosci Lett 206:33–36

    PubMed  CAS  Google Scholar 

  • Bennett HL, Gustafsson JA, Keast JR (2003) Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder. Auton Neurosci 105:90–100

    PubMed  CAS  Google Scholar 

  • Birder LA, de Groat WC (1993) Induction of c-fos expression in spinal neurons by nociceptive and nonnociceptive stimulation of LUT. Am J Physiol 265:R326–R333

    PubMed  CAS  Google Scholar 

  • Birder LA, de Groat WC (2007) Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol 4:46–54

    PubMed  CAS  Google Scholar 

  • Birder LA, Apodaca G, de Groat WC, Kanai AJ (1998) Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am J Physiol 275:F226–F229

    PubMed  CAS  Google Scholar 

  • Birder LA, Barrick S, Roppolo JR, Kanai A, de Groat WC, Kiss S, Buffington CA (2003) Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium Am J Physiol 285:F423–F429

    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

    PubMed  CAS  Google Scholar 

  • Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396–13401

    PubMed  CAS  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 (2002a) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860

    PubMed  CAS  Google Scholar 

  • Birder LA, Nealen ML, Kiss S, de Groat WC, Caterina MJ, Wang E, Apodaca G, Kanai AJ (2002b) Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci 22:8063–8070

    PubMed  CAS  Google Scholar 

  • Birder LA, Ruan HZ, Chopra B, Xiang Z, Barrick S, Buffington CA, Roppolo JR, Ford AP, de Groat WC, Burnstock G (2004) Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am J Physiol Renal Physiol 287:F1084–F1091

    PubMed  CAS  Google Scholar 

  • Birder LA, de Groat WC, Apodaca G (2008) Physiology of the urothelium. In: Schick E, Corcos J (eds) Textbook of the neurogenic bladder, 2nd edn. Taylor and Francis, London, chap 3

    Google Scholar 

  • Black JA, Cummins TR, Yoshimura N, de Groat WC, Waxman SG (2003) Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats. Brain Res 963:132–138

    PubMed  CAS  Google Scholar 

  • Brady CM, Apostolidis A, Yiangou Y, Baecker PA, Ford AP, Freeman A, Jacques TS, Fowler CJ, Anand P (2004a) P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol 46:247–253

    PubMed  CAS  Google Scholar 

  • Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P (2004b) 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

    PubMed  CAS  Google Scholar 

  • Chai TC, Steers WD, Broder SR, Rauchenwald M, Tuttle JB (1996) Characterization of laterality of innervation of the rat bladder. Scand J Urol Nephrol Suppl 179:87–92

    PubMed  CAS  Google Scholar 

  • Chai TC, Gray ML, Steers WD (1998) The incidence of a positive ice water test in bladder outlet obstructed patients: evidence for bladder neural plasticity. J Urol 160:34–38

    PubMed  CAS  Google Scholar 

  • Chang HY, Cheng CL, Chen JJ, de Groat WC (2007) 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

    PubMed  CAS  Google Scholar 

  • Charrua A, Cruz CD, Cruz F, Avelino A (2007) Transient receptor potential vanilloid subfamily 1 is essential for the generation of noxious bladder input and bladder overactivity in cystitis. J Urol 177:1537–1541

    PubMed  CAS  Google Scholar 

  • Cheng CL, Chai CY, de Groat WC (1997) Detrusor-sphincter dyssynergia induced by cold stimulation of the urinary bladder of rats. Am J Physiol 272:R1271–R1282

    PubMed  CAS  Google Scholar 

  • Cheng CL, Liu JC, Chang SY, Ma CP, de Groat WC (1999) Effect of capsaicin on the micturition reflex in normal and chronic spinal cord-injured cats. Am J Physiol 277:R786–R794

    PubMed  CAS  Google Scholar 

  • Chess-Williams R (2002) Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol 22:133–145

    PubMed  CAS  Google Scholar 

  • Chopra B, Barrick SR, Meyers S, Beckel JM, Zeidel ML, Ford AP, de Groat WC, Birder LA (2005) Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J Physiol 562:859–871

    PubMed  CAS  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, Fraser MO, Yu Y, Chancellor MB, de Groat WC, Yoshimura N (2001) The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J Urol 165:975–979

    PubMed  CAS  Google Scholar 

  • Clifton GL, Coggeshall RE, Vance WH, Willis WD (1976) Receptive fields of unmyelinated ventral root afferent fibres in the cat. J Physiol 256:573–600

    PubMed  CAS  Google Scholar 

  • Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407:1011–1015

    PubMed  CAS  Google Scholar 

  • Crowe R, Light K, Chilton CP, Burnstock G (1986) Vasoactive intestinal polypeptide-, somatostatin- and substance P-immunoreactive nerves in the smooth and striated muscle of the intrinsic external urethral sphincter of patients with spinal cord injury. J Urol 136:487–491

    PubMed  CAS  Google Scholar 

  • Cruz F, Dinis P (2007) Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms. Neurourol Urodyn 26:920–927

    PubMed  CAS  Google Scholar 

  • Cruz CD, Ferreira D, McMahon SB, Cruz F (2007) The activation of the ERK pathway contributes to the spinal c-fos expression observed after noxious bladder stimulation. Somatosens Mot Res 24:15–20

    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

    PubMed  CAS  Google Scholar 

  • Dang K, Bielefeldt K, Gebhart GF (2005) Differential responses of bladder lumbosacral and thoracolumbar dorsal root ganglion neurons to purinergic agonists, protons, and capsaicin. J Neurosci 25:3973–3984

    PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • de Groat WC (1989) Neuropeptides in pelvic afferent pathways. In: Polak JM (ed) Regulatory peptides. Birkhauser, Basel, pp 334–336

    Google Scholar 

  • de Groat WC (2004) The urothelium in overactive bladder: passive bystander or active participant? Urology 64:7–11

    PubMed  Google Scholar 

  • de Groat WC, Yoshimura N (2006) Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. Eds.: Weaver LC, Polosa C. Progress in Brain Research 152:59–84

    Google Scholar 

  • de Groat WC, Nadelhaft I, Milne RJ, Booth AM, Morgan C, Thor K (1981) Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Sys 3:135–160

    CAS  Google Scholar 

  • de Groat WC, Kawatani M, Hisamitsu T, Cheng C-L, Ma C-P, Thor K, Steers W, Roppolo JR (1990) Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auto Nerv Sys 30(Suppl):S71–S77

    Google Scholar 

  • de Groat WC, Booth AM and Yoshimura N (1993) Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA (ed) The autonomic nervous system, vol 3. Nervous control of the urogenital system. Harwood, London, pp 227–289

    Google Scholar 

  • de Groat WC, Fraser MO, Yoshiyama M, Smerin S, Tai C, Chancellor MB, Yoshimura N, Roppolo JR (2001) Neural control of the urethra. Scand J Urol Nephrol Suppl 207:35–43; discussion 106–125

    PubMed  Google Scholar 

  • Dickson A, Avelino A, Cruz F, Ribeiro-da-Silva A (2006) Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat urinary bladder in a chronic model of cyclophosphamide-induced cystitis. Neuroscience 139:671–685

    PubMed  CAS  Google Scholar 

  • Dinis P, Charrua A, Avelino A, Yaqoob M, Bevan S, Nagy I, Cruz F (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24:11253–11263

    PubMed  CAS  Google Scholar 

  • Dmitrieva N, McMahon SB (1996) Sensitisation of visceral afferents by nerve growth factor in the adult rat. Pain 66:87–97

    PubMed  CAS  Google Scholar 

  • Dmitrieva N, Shelton D, Rice AS, McMahon SB (1997) The role of nerve growth factor in a model of visceral inflammation. Neuroscience 78:449–459

    PubMed  CAS  Google Scholar 

  • Downie JW, Armour JA (1992) Mechanoreceptor afferent activity compared with receptor field dimensions and pressure changes in feline urinary bladder. Can J Physiol Pharmacol 70:1457–1467

    PubMed  CAS  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 

  • Everaerts W, Gevaert T, Nilius B, De Ridder D (2008) On the origin of bladder sensing: Tr(i)ps in urology. Neurourol Urodyn 27:264–273

    PubMed  CAS  Google Scholar 

  • Fahrenkrug J, Hannibal J (1998) Pituitary adenylate cyclase activating polypeptide immunor-eactivity in capsaicin-sensitive nerve fibres supplying the rat urinary tract. Neuroscience 83:1261–1272

    PubMed  CAS  Google Scholar 

  • Fall M, Lindström S, Mazieres L (1990) A bladder-to-bladder cooling reflex in the cat. J Physiol (Lond) 427:281–300

    CAS  Google Scholar 

  • Fam B, Yalla SV (1988) Vesicourethral dysfunction in spinal cord injury and its management. Semin Neurol 8:150–155

    PubMed  CAS  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 505:503–511

    PubMed  CAS  Google Scholar 

  • Floyd K, Hick VE, Morrison JF (1976) Mechanosensitive afferent units in the hypogastric nerve of the cat. J Physiol (Lond) 259:457–471

    CAS  Google Scholar 

  • Forrest SL, Keast JR (2008) Expression of receptors for glial cell line-derived neurotrophic factor family ligands in sacral spinal cord reveals separate targets of pelvic afferent fibers. J Comp Neurol 506:989–1002

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gabella G, Davis C (1998) Distribution of afferent axons in the bladder of rats. J Neurocytol 27:141–155

    PubMed  CAS  Google Scholar 

  • Geirsson G, Fall M, Lindstrom S (1993) The ice-water test – a simple and valuable supplement to routine cystometry. Br J Urol 71:681–685

    PubMed  CAS  Google Scholar 

  • Geirsson G, Fall M, Sullivan L (1995) Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia. J. Urol 154:1825–1829

    Google Scholar 

  • Geirsson G, Lindstrom S, Fall M, Gladh G, Hermansson G, Hjalmas K (1994) Positive bladder cooling test in neurologically normal young children. J Urol 151:446–448

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Gillespie JI, Markerink-van Ittersum M, de Vente J (2006) Sensory collaterals, intramural ganglia and motor nerves in the guinea-pig bladder: evidence for intramural neural circuits. Cell Tissue Res 325:33–45

    PubMed  CAS  Google Scholar 

  • Gold MS, Shuster MJ, Levine JD (1996) Characterization of six voltage-gated K+ currents in adult rat sensory neurons. J Neurophysiol 75:2629–2646

    PubMed  CAS  Google Scholar 

  • Gosling JA, Dixon JS, Critchley HO, Thompson SA (1981) A comparative study of the human external sphincter and periurethral levator ani muscles. Br J Urol 53:35–41

    PubMed  CAS  Google Scholar 

  • Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11:946–958

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

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

    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 

  • Hu P, Meyers S, Liang FX, Deng FM, Kachar B, Zeidel ML, Sun TT (2002) Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. Am J Physiol Renal Physiol 283:F1200–F1207

    PubMed  CAS  Google Scholar 

  • Hu VY, Zvara P, Dattilio A, Redman TL, Allen SJ, Dawbarn D, Stroemer RP, Vizzard MA (2005) Decrease in bladder overactivity with REN1820 in rats with cyclophosphamide induced cystitis. J Urol 173:1016–1021

    PubMed  Google Scholar 

  • Hulsebosch CE, Coggeshall RE (1982) An analysis of the axon populations in the nerves to the pelvic viscera in the rat. J Comp Neurol 211:1–10

    PubMed  CAS  Google Scholar 

  • Ishizuka O, Alm P, Larsson B, Mattiasson A, Andersson KE (1995) Facilitatory effect of pituitary adenylate cyclase activating polypeptide on micturition in normal, conscious rats. Neuroscience 66:1009–1014

    PubMed  CAS  Google Scholar 

  • Ito K, Iwami A, Katsura H, Ikeda M (2007) Therapeutic effects of the putative P2X(3)/P2X (2/3) antagonist A-317491 on cyclophosphamide-induced cystitis in rats. Naunyn Schmiedebergs Arch Pharmacol 377(4–6):483–490

    PubMed  Google Scholar 

  • Jaggar SI, Scott HC, Rice AS (1999) Inflammation of the rat urinary bladder is associated with a referred thermal hyperalgesia which is nerve growth factor dependent. Br J Anaesth 83: 442–448

    PubMed  CAS  Google Scholar 

  • Jancso G, Maggi CA (1987) Distribution of capsaicin-sensitive urinary bladder afferents in the rat spinal cord. Brain Res 418:371–376

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  • Jiang CH, Mazieres L, Lindstrom S (2002) Cold- and menthol-sensitive C afferents of cat urinary bladder. J Physiol 543:211–220

    PubMed  CAS  Google Scholar 

  • Johansson S, Fall M (1997) The pathology of interstitial cystitis. In: Sant GR (ed) Interstitial cystitis. Lippincott-Raven, Philadelphia, pp 143–151

    Google Scholar 

  • Kawatani M, Erdman SL, de Groat WC (1985) Vasoactive intestinal polypeptide and substance P in primary afferent pathways to the sacral spinal cord of the cat. J Comp Neurol 241:327–347

    PubMed  CAS  Google Scholar 

  • Kawatani M, Nagel J, de Groat WC (1986) Identification of neuropeptides in pelvic and pudendal nerve afferent pathways to the sacral spinal cord of the cat. J Comp Neurol 249:117–132

    PubMed  CAS  Google Scholar 

  • Kawatani M, Suzuki T, de Groat WC (1996) Corticotropin releasing factor-like immunoreactivity in afferent projections to the sacral spinal cord of the cat. J Auton Nerv Syst 61:218–226

    PubMed  CAS  Google Scholar 

  • Keast JR, de Groat WC (1992) Segmental distribution and peptide content of primary afferent neurons innervating the urogenital organs and colon of male rats. J Comp Neurol 319:615–623

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Kebapci N, Yenilmez A, Efe B, Entok E, Demirustu C (2007) Bladder dysfunction in type 2 diabetic patients. Neurourol Urodyn 26:814–819

    PubMed  Google Scholar 

  • Kruse MN, Bray LA, de Groat WC (1995) Influence of spinal cord injury on the morphology of bladder afferent and efferent neurons. J Auto Nerv Sys 54:215–224

    CAS  Google Scholar 

  • Kullmann FA, Artim D, Beckel J, Barrick S, de Groat WC, Birder LA (2008a) Heterogeneity of muscarinic receptor-mediated Ca2+ responses in cultured urothelial cells from rat. Am J Physiol Renal Physiol 294:F971–F981

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Langford LA, Coggeshall RE (1981) Branching of sensory axons in the peripheral nerve of the rat. J Comp Neurol 203:745–750

    Google Scholar 

  • Lanteri-Minet M, Bon K, de Pommery J, Michiels JF, Menetrey D (1995) Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-fos and Krox-24 proteins. Exp Brain Res 105:220–232

    PubMed  CAS  Google Scholar 

  • Lassmann G (1984) Muscle spindles and sensory nerve endings in the urethral sphincter. Acta Neuropathol 63:344–346

    PubMed  CAS  Google Scholar 

  • Lavelle J, Meyers S, Ramage R, Bastacky S, Doty D, Apodaca G, Zeidel ML (2002) Bladder permeability barrier: recovery from selective injury of surface epithelial cells. Am J Physiol Renal Physiol 283:F242–F253

    PubMed  CAS  Google Scholar 

  • Lawson SN, Perry MJ, Prabhakar E, McCarthy PW (1993) Primary sensory neurones: neurofilament, neuropeptides, and conduction velocity. Brain Res Bull 30:239–243

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Lazzeri M, Beneforti P, Spinelli M, Zanollo A, Barbagli G, Turini D (2000) Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. J Urol 164:676–679

    PubMed  CAS  Google Scholar 

  • Lee HY, Bardini M, Burnstock G (2000) Distribution of P2X receptors in the urinary bladder and the ureter of the rat. J Urol 163:2002–2007

    PubMed  CAS  Google Scholar 

  • Lindstrom S, Mazieres L, Jiang CH (2004) Inhibition of the bladder cooling reflex in the awake state: an experimental study in the cat. J Urol 172:2051–2053

    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(1):104–108

    PubMed  Google Scholar 

  • Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV, Osborne JL (1997) Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol 79:572–577

    PubMed  CAS  Google Scholar 

  • Maggi CA (1993) The dual, sensory and efferent function of the capsaicin-sensitive primary sensory nerves in the bladder and urethra. In: Maggi CA (ed) Nervous control of the urogenital system, vol 1. Harwood, London, pp 383–422

    Google Scholar 

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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Masuda H, Kim JH, Kihara K, Chancellor MB, de Groat WC, Yoshimura N (2007) Inhibitory roles of peripheral nitrergic mechanisms in capsaicin-induced detrusor overactivity in the rat. BJU Int 100:912–918

    PubMed  CAS  Google Scholar 

  • Mazieres L, Jiang C, Lindstrom S (1998) The C fibre reflex of the cat urinary bladder. J Physiol 513(2):531–541

    PubMed  Google Scholar 

  • McGuire EJ, Morrissey SG, Schichun Z, Horwinsk E (1983) Control of reflex detrusor activity in normal and spinal injured non-human primates. J Urol 129:197–199

    PubMed  CAS  Google Scholar 

  • Mitsui T, Kakizaki H, Matsuura S, Ameda K, Yoshioka M, Koyanagi T (2001) Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats. J Neurophysiol 86:2276–2284

    PubMed  CAS  Google Scholar 

  • Miura A, Kawatani M, de Groat WC (2001) Effects of pituitary adenylate cyclase activating polypeptide on lumbosacral preganglionic neurons in the neonatal rat spinal cord. Brain Res 895:223–232

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Morgan C, de Groat WC, Nadelhaft I (1986) The spinal distribution of sympathetic preganglionic and visceral primary afferent neurons that send axons into the hypogastric nerves of the cat. J Comp Neurol 243:23–40

    PubMed  CAS  Google Scholar 

  • Morgan CW, de Groat WC, Felkins LA, Zhang SJ (1993) Intracellular injection of neurobiotin or horseradish peroxidase reveals separate types of preganglionic neurons in the sacral parasympathetic nucleus of the cat. J Comp Neurol 331:161–182

    PubMed  CAS  Google Scholar 

  • Morgan CW, Ohara PT, Scott DE (1999) Vasoactive intestinal polypeptide in sacral primary sensory pathways in the cat. J Comp Neurol 407:381–394

    PubMed  CAS  Google Scholar 

  • Morrison JF (1997) The physiological mechanisms involved in bladder emptying. Scand J Urol Nephrol Suppl 184:15–18

    PubMed  CAS  Google Scholar 

  • Morrison JF, Birder L, Craggs M, de Groat WC, Downie JW, Drake M, Fowler CJ, Thor KB (2005) Neural control. In: Abrams P, Cardozo L, Khoury S, Wein A (eds) Incontinence. Health, Plymouth, pp 363–422

    Google Scholar 

  • Moss NG, Harrington WW, Tucker MS (1997) Pressure, volume, and chemosensitivity in afferent innervation of urinary bladder in rats. Am J Physiol 272:R695–R703

    PubMed  CAS  Google Scholar 

  • Murray E, Malley SE, Qiao LY, Hu VY, Vizzard MA (2004) Cyclophosphamide induced cystitis alters neurotrophin and receptor tyrosine kinase expression in pelvic ganglia and bladder. J Urol 172:2434–2439

    PubMed  CAS  Google Scholar 

  • Nadelhaft I, Vera PL (1992) Reduced urinary bladder afferent conduction velocities in streptozocin diabetic rats. Neurosci Lett 135:276–8

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Nishiguchi J, Sasaki K, Seki S, Chancellor MB, Erickson KA, de Groat WC, Kumon H, Yoshimura N (2004) Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation. Eur J Neurosci 20:474–482

    PubMed  Google Scholar 

  • Nishiguchi J, Hayashi Y, Chancellor MB, de Miguel F, de Groat WC, Kumon H, Yoshimura N (2005) Detrusor overactivity induced by intravesical application of adenosine 5′-triphosphate under different delivery conditions in rats. Urology 66:1332–1337

    PubMed  Google Scholar 

  • Noronha R, Akbarali H, Malykhina A, Foreman RD, Greenwood-Van Meerveld B (2007) Changes in urinary bladder smooth muscle function in response to colonic inflammation. Am J Physiol Renal Physiol 293:F1461–F1467

    PubMed  CAS  Google Scholar 

  • Novakovic SD, Tzoumaka E, McGivern JG, Haraguchi M, Sangameswaran L, Gogas KR, Eglen RM, Hunter JC (1998) Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions. J Neurosci 18:2174–2187

    PubMed  CAS  Google Scholar 

  • Ogawa T, Kamo I, Pflug BR, Nelson JB, Seki S, Igawa Y, Nishizawa O, de Groat WC, Chancellor MB, Yoshimura N (2004) Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats. J Urol 172:1533–1537

    PubMed  CAS  Google Scholar 

  • Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT, Haak-Frendscho M (1999) Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol 161:438–442

    PubMed  CAS  Google Scholar 

  • Ozawa H, Chancellor MB, Jung SY, Yokoyama T, Fraser MO, Yu Y, de Groat WC, Yoshimura N (1999) Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis. J Urol 162:2211–2216

    PubMed  CAS  Google Scholar 

  • Pandita RK, Andersson KE (2002) Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. J Urol 168:1230–1234

    PubMed  CAS  Google Scholar 

  • Pandita RK, Mizusawa H, Andersson KE (2000) Intravesical oxyhemoglobin initiates bladder overactivity in conscious, normal rats. J Urol 164:545–550

    PubMed  CAS  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

    PubMed  CAS  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 

  • Popat R, Apostolidis A, Kalsi V, Gonzales G, Fowler CJ, Dasgupta P (2005) A comparison between the response of patients with idiopathic detrusor overactivity and neurogenic detrusor overactivity to the first intradetrusor injection of botulinum-A toxin. J Urol 174:984–989

    PubMed  CAS  Google Scholar 

  • Qiao LY, Vizzard MA (2002) Cystitis-induced upregulation of tyrosine kinase (TrkA, TrkB) receptor expression and phosphorylation in rat micturition pathways. J Comp Neurol 454: 200–211

    PubMed  CAS  Google Scholar 

  • Qiao LY, Vizzard MA (2004) Up-regulation of phosphorylated CREB but not c-Jun in bladder afferent neurons in dorsal root ganglia after cystitis. J Comp Neurol 469:262–274

    PubMed  CAS  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 

  • Rockswold GL, Bradley WE, Chou SN (1980a) Innervation of the external urethral and external anal sphincters in higher primates. J Comp Neurol 193:521–528

    PubMed  CAS  Google Scholar 

  • Rockswold GL, Bradley WE, Chou SN (1980b) Innervation of the urinary bladder in higher primates. J Comp Neurol 193:509–520

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Roppolo JR, Tai C, Booth AM, Buffington CA, de Groat WC, Birder LA (2005) Bladder Aδ afferent nerve activity in normal cats and cats with feline interstitial cystitis. J Urol 173:1011–1015

    PubMed  Google Scholar 

  • Sasaki K, Chancellor MB, Phelan MW, Yokoyama T, Fraser MO, Seki S, Kubo K, Kumon H, de Groat WC, Yoshimura N (2002) Diabetic cystopathy correlates with long-term decrease in nerve growth factor (NGF) levels in the bladder and lumbosacral dorsal root ganglia. J Urol 168:1259–1264

    PubMed  Google Scholar 

  • Sasaki K, Chancellor MB, Goins WF, Phelan MW, Glorioso JC, de Groat WC, Yoshimura N (2004) Gene therapy using replication-defective herpes simplex virus vectors expressing nerve growth factor in a rat model of diabetic cystopathy. Diabetes 53:2723–2730

    PubMed  CAS  Google Scholar 

  • Satchell P, Vaughan C (1994) Bladder wall tension and mechanoreceptor discharge. Pflugers Arch 426:304–309

    PubMed  CAS  Google Scholar 

  • Schurch B, de Seze M, Denys P, Chartier-Kastler E, Haab F, Everaert K, Plante P, Perrouin-Verbe B, Kumar C, Fraczek S, Brin MF (2005) Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J Urol 174:196–200

    PubMed  CAS  Google Scholar 

  • Schurch B, Denys P, Kozma CM, Reese PR, Slaton T, Barron RL (2007) Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence. Eur Urol 52:850–858

    PubMed  CAS  Google Scholar 

  • Sculptoreanu A, de Groat WC (2003) Protein kinase C is involved in neurokinin receptor modulation of N- and L-type Ca2+ channels in DRG neurons of the adult rat. J Neurophysiol 90:21–31

    PubMed  CAS  Google Scholar 

  • Sculptoreanu A, de Groat WC (2007) Neurokinins enhance excitability in capsaicin-responsive DRG neurons. Exp Neurol 205:92–100

    PubMed  CAS  Google Scholar 

  • Sculptoreanu A, de Groat WC, Buffington CA, Birder LA (2005a) Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline interstitial cystitis. Exp Neurol 193:437–443

    PubMed  Google Scholar 

  • Sculptoreanu A, de Groat WC, Buffington CA, Birder LA (2005b) Protein kinase C contributes to abnormal capsaicin responses in DRG neurons from cats with feline interstitial cystitis. Neurosci Lett 381:42–46

    PubMed  CAS  Google Scholar 

  • Seki S, Sasaki K, Fraser MO, Igawa Y, Nishizawa O, Chancellor MB, de Groat WC, Yoshimura N (2002) Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. J Urol 168:2269–2274

    PubMed  CAS  Google Scholar 

  • Seki S, Sasaki K, Igawa Y, Nishizawa O, Chancellor M, de Groat W, Yoshimura N (2003) Detrusor overactivity induced by increased levels of nerve growth factor in bladder afferent pathways in rats. Neurourol Urodyn 22:375–377

    Google Scholar 

  • Seki S, Sasaki K, Igawa Y, Nishizawa O, Chancellor MB, de Groat WC, Yoshimura N (2004) Suppression of detrusor-sphincter dyssynergia by immunoneutralization of nerve growth factor in lumbosacral spinal cord in spinal cord injured rats. J Urol 171:478–482

    PubMed  Google Scholar 

  • Seki S, Erickson KA, Seki M, Nishizawa O, Igawa Y, Ogawa T, de Groat WC, Chancellor MB, Yoshimura N (2005) Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation. Am J Physiol Renal Physiol 288:F466–F473

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Smet PJ, Moore KH, Jonavicius J (1997) Distribution and colocalization of calcitonin gene-related peptide, tachykinins, and vasoactive intestinal peptide in normal and idiopathic unstable human urinary bladder. Lab Invest 77:37–49

    PubMed  CAS  Google Scholar 

  • Steers WD, Tuttle JB (2006) Mechanisms of disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol 3:101–110

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Steers WD, Kolbeck S, Creedon D, Tuttle JB (1991b) Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest 88:1709–1715

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Steers WD, Creedon DJ, Tuttle JB (1996) Immunity to nerve growth factor prevents afferent plasticity following urinary bladder hypertrophy. J Urol 155:379–385

    PubMed  CAS  Google Scholar 

  • Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 172:1175–1178

    PubMed  CAS  Google Scholar 

  • Stewart T, Beyak MJ, Vanner S (2003) Ileitis modulates potassium and sodium currents in guinea pig dorsal root ganglia sensory neurons. J Physiol 552:797–807

    PubMed  CAS  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 53:391–400

    PubMed  CAS  Google Scholar 

  • Studeny S, Torabi A, Vizzard MA (2005) P2X2 and P2X3 receptor expression in postnatal and adult rat urinary bladder and lumbosacral spinal cord. Am J Physiol Regul Integr Comp Physiol 289:R1155–R1168

    PubMed  CAS  Google Scholar 

  • Su X, Sengupta JN, Gebhart GF (1997) Effects of opioids on mechanosensitive pelvic nerve afferent fibers innervating the urinary bladder of the rat. J Neurophysiol 77:1566–1580

    PubMed  CAS  Google Scholar 

  • Sun Y, Keay S, De Deyne PG, Chai TC (2001) Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. J Urol 166:1951–1956

    Google Scholar 

  • Tainio H (1993) Neuropeptidergic innervation of the human male distal urethra and intrinsic external urethral sphincter. Acta Histochem 94:197–201

    PubMed  CAS  Google Scholar 

  • Tempest HV, Dixon AK, Turner WH, Elneil S, Sellers LA, Ferguson DR (2004) P2X and P2X receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int 93:1344–1348

    PubMed  CAS  Google Scholar 

  • Thor K, Kawatani M, de Groat WC (1986) Plasticity in the reflex pathways to the lower urinary tract of the cat during postnatal development and following spinal cord injury. In: Goldberger M, Gorio A, Murray M (eds) Development and plasticity of the mammalian spinal cord. Fidia research series, vol III. Fidia, Padua, pp 65–81

    Google Scholar 

  • Thor KB, Hisamitsu T, Roppolo JR, Tuttle P, Nagel J, de Groat WC (1989a) Selective inhibitory effects of ethylketocyclazocine on reflex pathways to the external urethral sphincter of the cat. J Pharmacol Exp Ther 248:1018–1025

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Tong YC, Cheng JT (2007) Aldose reductase inhibitor ONO-2235 restores the alterations of bladder nerve growth factor and neurotrophin receptor p75 genetic expression in streptozotocin induced diabetic rats. J Urol 178:2203–7

    PubMed  CAS  Google Scholar 

  • Uemura E, Fletcher TF, Dirks VA, Bradley WE (1973) Distribution of sacral afferent axons in cat urinary bladder. Am J Anat 136:305–313

    PubMed  CAS  Google Scholar 

  • Uemura E, Fletcher TF, Bradley WE (1975) Distribution of lumbar and sacral afferent axons in submucosa of cat urinary bladder. Anat Rec 183:579–587

    PubMed  CAS  Google Scholar 

  • Ueyama T, Mizuno N, Nomura S, Konishi A, Itoh K, Arakawa H (1984) Central distribution of afferent and efferent components of the pudendal nerve in cat. J Comp Neurol 222:38–46

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Uvelius B, Gabella G (1998) The distribution of intramural nerves in urinary bladder after partial denervation in the female rat. Urol Res 26:291–297

    PubMed  CAS  Google Scholar 

  • Vera PL, Nadelhaft I (1990) Conduction velocity distribution of afferent fibers innervating the rat urinary bladder. Brain Res 520:83–89

    PubMed  CAS  Google Scholar 

  • Vizzard MA (2000a) Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury. Am J Physiol Regul Integr Comp Physiol 279:R295–R305

    PubMed  CAS  Google Scholar 

  • Vizzard MA (2000b) Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol 161:273–284

    PubMed  CAS  Google Scholar 

  • Vizzard MA (2001) Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis. J Chem Neuroanat 21:125–138

    PubMed  CAS  Google Scholar 

  • Vizzard MA (2006) Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury. Prog Brain Res 152:97–115

    PubMed  CAS  Google Scholar 

  • Vizzard MA, Boyle MM (1999) Increased expression of growth-associated protein (GAP-43) in lower urinary tract pathways following cyclophosphamide (CYP)-induced cystitis. Brain Res 844:174–187

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Vulchanova L, Riedl MS, Shuster SJ, Stone LS, Hargreaves KM, Buell G, Surprenant A, North RA, Elde R (1998) P2X3 is expressed by DRG neurons that terminate in inner lamina II. Eur J Neurosci 10:3470–3478

    PubMed  CAS  Google Scholar 

  • Waddell PJ, Lawson SN (1990) Electrophysiological properties of subpopulations of rat dorsal root ganglion neurons in vitro. Neuroscience 36:811–822

    PubMed  CAS  Google Scholar 

  • Wang EC, Lee JM, Johnson JP, Kleyman TR, Bridges R, Apodaca G (2003) Hydrostatic pressure-regulated ion transport in bladder uroepithelium. Am J Physiol Renal Physiol 285:F651–F663

    PubMed  CAS  Google Scholar 

  • Wang ZY, Wang P, Merriam FV, Bjorling DE (2008) Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. Pain 139(1):158–167

    PubMed  CAS  Google Scholar 

  • Weaver LC, Marsh DR, Gris D, Brown A, Dekaban GA (2006) Autonomic dysreflexia after spinal cord injury: central mechanisms and strategies for prevention. Prog Brain Res 152:245–263

    PubMed  Google Scholar 

  • Winter DL (1971) Receptor characteristics and conduction velocites in bladder afferents. J Psych Res 8:225–235

    CAS  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 

  • Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A (2004) Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63:17–23

    PubMed  Google Scholar 

  • Yoshimura N (1999) Bladder afferent pathway and spinal cord injury: possible mechanisms inducing hyperreflexia of the urinary bladder. Prog Neurobiol 57:583–606

    PubMed  CAS  Google Scholar 

  • Yoshimura N, de Groat WC (1997) Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury. J Physiol 503:269–276

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Yoshimura N, White G, Weight FF, de Groat WC (1996) Different types of Na+ and A-type K+ and A-type K+ currents in dorsal root ganglion neurons innervating the rat urinary bladder. J Physiol 494:1–16

    PubMed  CAS  Google Scholar 

  • Yoshimura N, Erdman SL, Snider MW, de Groat WC (1998) Effects of spinal cord injury on neurofilament immunoreactivity and capsaicin sensitivity in rat dorsal root ganglion neurons innervating the urinary bladder. Neuroscience 83:633–643

    PubMed  CAS  Google Scholar 

  • Yoshimura N, Seki S, de Groat WC (2001a) Nitric oxide modulates Ca2+ channels in dorsal root ganglion neurons rat urinary bladder. J Neurophysiol 86:304–311

    PubMed  CAS  Google Scholar 

  • Yoshimura N, Seki S, Novakovic SD, Tzoumaka E, Erickson VL, Erickson KA, Chancellor MB, de Groat WC (2001b) The involvement of the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3/SNS) in a rat model of visceral pain. J Neurosci 21:8690–8696

    PubMed  CAS  Google Scholar 

  • Yoshimura N, Seki S, Erickson KA, Erickson VL, Chancellor 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

    PubMed  CAS  Google Scholar 

  • Yoshimura N, Chancellor MB, Andersson KE, Christ GJ (2005) Recent advances in understanding the biology of diabetes-associated bladder complications and novel therapy. BJU Int 95: 733–738

    PubMed  Google Scholar 

  • Yoshimura N, Bennett NE, Hayashi Y, Ogawa T, Nishizawa O, Chancellor MB, de Groat WC, Seki S (2006) Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats. J Neurosci 26:10847–10855

    PubMed  CAS  Google Scholar 

  • Yoshiyama M, de Groat WC (2008a) Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords. Exp Neurol 211:449–455

    PubMed  CAS  Google Scholar 

  • Yoshiyama M, de Groat WC (2008b) The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase activating polypeptide in the neural pathways controlling the lower urinary tract. J Mol Neurosci 36(1–3):227–240

    PubMed  CAS  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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Zhong Y, Banning AS, Cockayne DA, Ford AP, Burnstock G, McMahon SB (2003) Bladder and cutaneous sensory neurons of the rat express different functional P2X receptors. Neuroscience 120:667–675

    PubMed  CAS  Google Scholar 

  • Zvara P, Braas KM, May V, Vizzard MA (2006) A role for pituitary adenylate cyclase activating polypeptide (PACAP) in detrusor hyperreflexia after spinal cord injury (SCI). Ann N Y Acad Sci 1070:622–628

    PubMed  CAS  Google Scholar 

  • Zvara P, Vizzard MA (2007) Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord. BMC Physiol 7:1–11

    Google Scholar 

  • Zvarova K, Dunleavy JD, Vizzard MA (2005) Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury. Exp Neurol 192:46–59

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William C. de Groat .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

de Groat, W.C., Yoshimura, N. (2009). Afferent Nerve Regulation of Bladder Function in Health and Disease. In: Canning, B., Spina, D. (eds) Sensory Nerves. Handbook of Experimental Pharmacology, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79090-7_4

Download citation

Publish with us

Policies and ethics