Skip to main content

Advertisement

Log in

Role of neurogenic inflammation in local communication in the visceral mucosa

Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions. For example, the urinary bladder urothelial cells are emerging as key elements in the detection and transmission of both physiological and nociceptive stimuli in the lower urinary tract. There is mounting evidence that these cells are involved in sensory mechanisms and can release mediators. Further, localization of afferent nerves next to the urothelium suggests these cells may be targets for transmitters released from bladder nerves and that chemicals released by urothelial cells may alter afferent excitability. Modifications of this type of communication in a number of pathological conditions can result in altered release of epithelial-derived mediators, which can activate local sensory nerves. Taken together, these and other findings highlighted in this review suggest that neurogenic inflammation involves complex anatomical and physiological interactions among a number of cell types in the bladder wall. The specific factors and pathways that mediate inflammatory responses in both acute and chronic conditions are not well understood and need to be further examined. Elucidation of mechanisms impacting on these pathways may provide insights into the pathology of various types of disorders involving the pelvic viscera.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Grover S, Srivastava A, Lee R, Tewari AK, Te AE (2011) Role of inflammation in bladder function and interstitial cystitis. Ther Adv Urol 3(1):19–33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Elbadawi AE, Light JK (1996) Distinctive ultrastructural pathology of nonulcerative interstitial cystitis: new observations and their potential significance in pathogenesis. Urol Int 56(3):137–162

    Article  PubMed  CAS  Google Scholar 

  3. Brookoff D (2009) Genitourinary pain syndromes: interstitial cystitis, chronic prostatitis, pelvic floor dysfunction, and related disorders. In: Smith HS (ed) Current Therapy in Pain. Saunders-Elsevier, Philadelphia, p 209–215

  4. Manikandan R, Kumar S, Dorairajan LN (2010) Hemorrhagic cystitis: a challenge to the urologist. Indian J Urol 26(2):159–166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Taweel WA, Seyam R (2015) Neurogenic bladder in spinal cord injury patients. Res Rep Urol 7:85–99

    PubMed  PubMed Central  Google Scholar 

  6. Cruz F (1998) Desensitization of bladder sensory fibers by intravesical capsaicin or capsaicin analogs. A new strategy for treatment of urge incontinence in patients with spinal detrusor hyperreflexia or bladder hypersensitivity disorders. Int Urogynecol J Pelvic Floor Dysfunct 9(4):214–220

    Article  PubMed  CAS  Google Scholar 

  7. Ham BK, Kim JH, Oh MM, Lee JG, Bae JH (2012) Effects of combination treatment of intravesical resiniferatoxin instillation and hydrodistention in patients with refractory painful bladder syndrome/interstitial cystitis: a pilot study. Int Neurourol J 16(1):41–46

    Article  PubMed  PubMed Central  Google Scholar 

  8. Birder L, Andersson KE (2013) Urothelial signaling. Physiol Rev 93(2):653–680

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Cheng F, Birder LA, Kullmann FA, Hornsby J, Watton PN, Watkins S, Thompson M, Robertson AM (2018) Layer-dependent role of collagen recruitment during loading of the rat bladder wall. Biomech Model Mechanobiol 17:403–417

  10. de Groat WC, Griffiths D, Yoshimura N (2015) Neural control of the lower urinary tract. Compr Physiol 5(1):327–396

    PubMed  PubMed Central  Google Scholar 

  11. de Groat WC, Yoshimura N (2015) Anatomy and physiology of the lower urinary tract. Handb Clin Neurol 130:61–108

    Article  PubMed  Google Scholar 

  12. Cohen RJ, Garrett K, Golding JL, Thomas RB, McNeal JE (2002) Epithelial differentiation of the lower urinary tract with recognition of the minor prostatic glands. Hum Pathol 33(9):905–909

  13. Andersson KE, McCloskey KD (2014) Lamina propria: the functional center of the bladder? Neurourol Urodyn 33(1):9–16

    Article  PubMed  Google Scholar 

  14. McCloskey KD (2011) Interstitial cells of Cajal in the urinary tract. Handb Exp Pharmacol 202:233–254

    Article  CAS  Google Scholar 

  15. Wiseman OJ, Fowler CJ, Landon DN (2003) The role of the human bladder lamina propria myofibroblast. BJU Int 91(1):89–93

    Article  PubMed  CAS  Google Scholar 

  16. Gabella G, Davis C (1998) Distribution of afferent axons in the bladder of rats. J Neurocytol 27(3):141–155

    Article  PubMed  CAS  Google Scholar 

  17. Danziger ZC, Grill WM (2016) Sensory and circuit mechanisms mediating lower urinary tract reflexes. Auton Neurosci 200:21–28

    Article  PubMed  Google Scholar 

  18. 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

  19. Kullmann FA, Chang HH, Gauthier C, McDonnell BM, Yeh JC, Clayton DR, Kanai AJ, de Groat WC, Apodaca GL, Birder LA (2017) Serotonergic paraneurons in the female mouse urethral epithelium and their potential role in peripheral sensory information processing. Acta Physiol 222(2). https://doi.org/10.1111/apha.1291

  20. Barry CM, Ji E, Sharma H, Yap P, Spencer NJ, Matusica D, Haberberger RV (2017) Peptidergic nerve fibers in the urethra: morphological and neurochemical characteristics in female mice of reproductive age. Neurourol Urodyn. https://doi.org/10.1002/nau.23434

  21. Maggi CA, Santicioli P, Geppetti P, Patacchini R, Frilli S, Astolfi M, Fusco B, Meli A (1988) Simultaneous release of substance P- and calcitonin gene-related peptide (CGRP)-like immunoreactivity from isolated muscle of the guinea pig urinary bladder. Neurosci Lett 87(1-2):163–167

    Article  PubMed  CAS  Google Scholar 

  22. Koltzenburg M, McMahon SB (1986) Plasma extravasation in the rat urinary bladder following mechanical, electrical and chemical stimuli: evidence for a new population of chemosensitive primary sensory afferents. Neurosci Lett 72(3):352–356

    Article  PubMed  CAS  Google Scholar 

  23. Yu Y, Fraser MO, de Groat WC (2004) Effects of ZD6169, a K ATP channel opener, on neurally-mediated plasma extravasation in the rat urinary bladder induced by chemical or electrical stimulation of nerves. Brain Res 996(1):41–46

    Article  PubMed  CAS  Google Scholar 

  24. Bjorling DE, Jerde TJ, Zine MJ, Busser BW, Saban MR, Saban R (1999) Mast cells mediate the severity of experimental cystitis in mice. J Urol 162(1):231–236

    Article  PubMed  CAS  Google Scholar 

  25. Bjorling DE, Saban MR, Saban R (1994) Neurogenic inflammation of guinea-pig bladder. Mediat Inflamm 3(3):189–197

    Article  CAS  Google Scholar 

  26. Ruggieri MR, Filer-Maerten S, Hieble JP, Hay DW (2000) Role of neurokinin receptors in the behavioral effect of intravesical antigen infusion in guinea pig bladder. J Urol 164(1):197–202

    Article  PubMed  CAS  Google Scholar 

  27. Ahluwalia A, Giuliani S, Scotland R, Maggi CA (1998) Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats. Br J Pharmacol 124(1):190–196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Pinter E, Szolcsanyi J (1995) Plasma extravasation in the skin and pelvic organs evoked by antidromic stimulation of the lumbosacral dorsal roots of the rat. Neuroscience 68(2):603–614

    Article  PubMed  CAS  Google Scholar 

  29. Jasmin L, Janni G, Ohara PT, Rabkin SD (2000) CNS induced neurogenic cystitis is associated with bladder mast cell degranulation in the rat. J Urol 164(3 Pt 1):852–855

    Article  PubMed  CAS  Google Scholar 

  30. Rudick CN, Pavlov VI, Chen MC, Klumpp DJ (2012) Gender specific pelvic pain severity in neurogenic cystitis. J Urol 187(2):715–724

    Article  PubMed  Google Scholar 

  31. Jasmin L, Janni G (2003) Experimental neurogenic cystitis. Adv Exp Med Biol 539(Pt A):319–335

    PubMed  Google Scholar 

  32. Spanos C, Pang X, Ligris K, Letourneau R, Alferes L, Alexacos N, Sant GR, Theoharides TC (1997) Stress-induced bladder mast cell activation: implications for interstitial cystitis. J Urol 157(2):669–672

    Article  PubMed  CAS  Google Scholar 

  33. Smith AL, Leung J, Kun S, Zhang R, Karagiannides I, Raz S, Lee U, Glovatscka V, Pothoulakis C, Bradesi S, Mayer EA, Rodriguez LV (2011) The effects of acute and chronic psychological stress on bladder function in a rodent model. Urology 78(4):967 e1–967 e7

    Article  Google Scholar 

  34. Mingin GC, Peterson A, Erickson CS, Nelson MT, Vizzard MA (2014) Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice. Am J Phys Regul Integr Comp Phys 307(7):R893–R900

    CAS  Google Scholar 

  35. Chang A, Butler S, Sliwoski J, Valentino R, Canning D, Zderic S (2009) Social stress in mice induces voiding dysfunction and bladder wall remodeling. Am J Physiol Ren Physiol 297(4):F1101–F1108

    Article  CAS  Google Scholar 

  36. Buffington CA (2011) Idiopathic cystitis in domestic cats—beyond the lower urinary tract. J Vet Intern Med 25(4):784–796

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Brady CM, Apostolidis A, Yiangou Y, Baecker PA, Ford AP, Freeman A, Jacques TS, Fowler CJ, Anand P (2004) P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur Urol 46(2):247–253

    Article  PubMed  CAS  Google Scholar 

  38. De Ridder D, Chandiramani V, Dasgupta P, Van Poppel H, Baert L, Fowler CJ (1997) Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J Urol 158(6):2087–2092

    Article  PubMed  Google Scholar 

  39. Sculptoreanu A, de Groat WC, Buffington CA, Birder LA (2005) Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline interstitial cystitis. Exp Neurol 193(2):437–443

    Article  PubMed  Google Scholar 

  40. Roppolo JR, Tai C, Booth AM, Buffington CA, de Groat WC, Birder LA (2005) Bladder Adelta afferent nerve activity in normal cats and cats with feline interstitial cystitis. J Urol 173(3):1011–1015

    Article  PubMed  Google Scholar 

  41. Gao Y, Zhang R, Chang HH, Rodriguez LV (2017) The role of C-fibers in the development of chronic psychological stress induced enhanced bladder sensations and nociceptive responses: a multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study. Neurourol Urodyn. https://doi.org/10.1002/nau.23374

  42. de Groat WC, Yoshimura N (2010) Changes in afferent activity after spinal cord injury. Neurourol Urodyn 29(1):63–76

    Article  PubMed  PubMed Central  Google Scholar 

  43. de Groat WC, Yoshimura N (2012) Plasticity in reflex pathways to the lower urinary tract following spinal cord injury. Exp Neurol 235(1):123–132

    Article  PubMed  Google Scholar 

  44. Yoshimura N, de Groat WC (1997) Plasticity of Na+ channels in afferent neurones innervating rat urinary bladder following spinal cord injury. J Physiol 503(Pt 2):269–276

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Cheng CL, Ma CP, de Groat WC (1995) Effect of capsaicin on micturition and associated reflexes in chronic spinal rats. Brain Res 678(1-2):40–48

    Article  PubMed  CAS  Google Scholar 

  46. Natura G, von Banchet GS, Schaible HG (2005) Calcitonin gene-related peptide enhances TTX-resistant sodium currents in cultured dorsal root ganglion neurons from adult rats. Pain 116(3):194–204

    Article  PubMed  CAS  Google Scholar 

  47. Moraes ER, Kushmerick C, Naves LA (2014) Characteristics of dorsal root ganglia neurons sensitive to Substance P. Mol Pain 10:73

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. de Groat WC, Yoshimura N (2006) Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury. Prog Brain Res 152:59–84

    Article  PubMed  CAS  Google Scholar 

  49. Christmas TJ, Rode J, Chapple CR, Milroy EJ, Turner-Warwick RT (1990) Nerve fibre proliferation in interstitial cystitis. Virchows Arch A Pathol Anat Histopathol 416(5):447–451

    Article  PubMed  CAS  Google Scholar 

  50. Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC (1995) Increased number of substance P positive nerve fibres in interstitial cystitis. Br J Urol 75(6):744–750

    Article  PubMed  CAS  Google Scholar 

  51. 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(6):770–776

  52. Schneider H, Wilbrandt K, Ludwig M, Beutel M, Weidner W (2005) Prostate-related pain in patients with chronic prostatitis/chronic pelvic pain syndrome. BJU Int 95(2):238–243

    Article  PubMed  Google Scholar 

  53. Lee UJ, Ackerman AL, Wu A, Zhang R, Leung J, Bradesi S, Mayer EA, Rodriguez LV (2015) Chronic psychological stress in high-anxiety rats induces sustained bladder hyperalgesia. Physiol Behav 139:541–548

    Article  PubMed  CAS  Google Scholar 

  54. Robbins M, DeBerry J, Ness T (2007) Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats. Physiol Behav 91(5):544–550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Latremoliere A, Woolf CJ (2009) Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 10(9):895–926

    Article  PubMed  PubMed Central  Google Scholar 

  56. Birder LA, Wolf-Johnston AS, Chib MK, Buffington CA, Roppolo JR, Hanna-Mitchell AT (2010) Beyond neurons: Involvement of urothelial and glial cells in bladder function. Neurourol Urodyn 29(1):88–96

    Article  PubMed  PubMed Central  Google Scholar 

  57. Dodds KN, Beckett EA, Evans SF, Grace PM, Watkins LR, Hutchinson MR (2016) Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain. Transl Psychiatry 6(9):e888

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Farmer MA, Huang L, Martucci K, Yang CC, Maravilla KR, Harris RE, Clauw DJ, Mackey S, Ellingson BM, Mayer EA, Schaeffer AJ, Apkarian AV, Network MR (2015) Brain white matter abnormalities in female interstitial cystitis/bladder pain syndrome: a MAPP network neuroimaging study. J Urol 194(1):118–126

    Article  PubMed  PubMed Central  Google Scholar 

  59. Deutsch G, Deshpande H, Frolich MA, Lai HH, Ness TJ (2016) Bladder distension increases blood flow in pain related brain structures in subjects with interstitial cystitis. J Urol 196(3):902–910

    Article  PubMed  PubMed Central  Google Scholar 

  60. Pandita RK, Andersson KE (2002) Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats. J Urol 168(3):1230–1234

    Article  PubMed  CAS  Google Scholar 

  61. Aizawa N, Igawa Y, Andersson KE, Iijima K, Nishizawa O, Wyndaele JJ (2011) Effects of intravesical instillation of ATP on rat bladder primary afferent activity and its relationship with capsaicin-sensitivitiy. Neurourol Urodyn 30:163–168

    Article  PubMed  CAS  Google Scholar 

  62. 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. 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(15):5670–5677

    Article  PubMed  CAS  Google Scholar 

  64. Smith CP, Vemulakonda VM, Kiss S, Boone TB, Somogyi GT (2005) Enhanced ATP release from rat bladder urothelium during chronic bladder inflammation: effect of botulinum toxin A. Neurochem Int 47(4):291–297

    Article  PubMed  CAS  Google Scholar 

  65. Kumar V, Chapple CR, Surprenant AM, Chess-Williams R (2007) Enhanced adenosine triphosphate release from the urothelium of patients with painful bladder syndrome: a possible pathophysiological explanation. J Urol 178(4 Pt 1):1533–1536

    Article  PubMed  CAS  Google Scholar 

  66. Sun Y, Chai TC (2006) Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis. Am J Phys Cell Phys 290(1):C27–C34

    Article  CAS  Google Scholar 

  67. Birder LA, Barrick SR, Roppolo JR, Kanai AJ, 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 Renal Physiol 285(3):F423–F429

    Article  PubMed  CAS  Google Scholar 

  68. 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 Ren Physiol 287(5):F1084–F1091

    Article  CAS  Google Scholar 

  69. 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(9):1344–1348

    Article  PubMed  CAS  Google Scholar 

  70. Sun Y, Chai TC (2004) Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171(1):448–452

    Article  PubMed  CAS  Google Scholar 

  71. 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(1):49–59

    Article  PubMed  CAS  Google Scholar 

  72. 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(6807):1011–1015

    Article  PubMed  CAS  Google Scholar 

  73. Kullmann FA, Wells GI, Langdale CL, Zheng J, Thor KB (2013) Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats. PLoS One 8(9):e73771

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Gevaert T, De Vos R, Everaerts W, Libbrecht L, Van Der Aa F, van den Oord J, Roskams T, De Ridder D (2011) Characterization of upper lamina propria interstitial cells in bladders from patients with neurogenic detrusor overactivity and bladder pain syndrome. J Cell Mol Med 15(12):2586–2593

    Article  PubMed  PubMed Central  Google Scholar 

  75. Chun SY, Lim GJ, Kwon TG, Kwak EK, Kim BW, Atala A, Yoo JJ (2007) Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials 28(29):4251–4256

    Article  PubMed  CAS  Google Scholar 

  76. Browne C, Davis NF, Mac Craith E, Lennon GM, Mulvin DW, Quinlan DM, Mc Vey GP, Galvin DJ (2015) A narrative review on the pathophysiology and management for radiation cystitis. Ther Adv Urol 2015:346812

    CAS  Google Scholar 

  77. Zwaans BM, Krueger S, Bartolone SN, Chancellor MB, Marples B, Lamb LE (2016) Modeling of chronic radiation-induced cystitis in mice. Adv Radiat Oncol 1(4):333–343

    Article  PubMed  PubMed Central  Google Scholar 

  78. Foditsch EE, Roider K, Patras I, Hutu I, Bauer S, Janetschek G, Zimmermann R (2017) Structural changes of the urinary bladder after chronic complete spinal cord injury in minipigs. Int Neurourol J 21(1):12–19

    Article  PubMed  PubMed Central  Google Scholar 

  79. Deveaud CM, Macarak EJ, Kucich U, Ewalt DH, Abrams WR, Howard PS (1998) Molecular analysis of collagens in bladder fibrosis. J Urol 160(4):1518–1527

    Article  PubMed  CAS  Google Scholar 

  80. Ochodnicky P, Cruz CD, Yoshimura N, Cruz F (2012) Neurotrophins as regulators of urinary bladder function. Nat Rev Urol 9(11):628–637

    Article  PubMed  CAS  Google Scholar 

  81. Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139(2):267–284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Bjorling DE, Jacobsen HE, Blum JR, Shih A, Beckman M, Wang ZY, Uehling DT (2001) Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor. BJU Int 87(7):697–702

    Article  PubMed  CAS  Google Scholar 

  83. Cruz CD (2014) Neurotrophins in bladder function: what do we know and where do we go from here? Neurourol Urodyn 33(1):39–45

    Article  PubMed  CAS  Google Scholar 

  84. Chen W, Ye DY, Han DJ, Fu GQ, Zeng X, Lin W, Liang Y (2016) Elevated level of nerve growth factor in the bladder pain syndrome/interstitial cystitis: a meta-analysis. Springerplus 5(1):1072

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Liu HT, Kuo HC (2012) Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease. PLoS One 7(9):e44687

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Dmitrieva N, Shelton D, Rice AS, McMahon SB (1997) The role of nerve growth factor in a model of visceral inflammation. Neuroscience 78(2):449–459

    Article  PubMed  CAS  Google Scholar 

  87. 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 7:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Schnegelsberg B, Sun TT, Cain G, Bhattacharya A, Nunn PA, Ford AP, Vizzard MA, Cockayne DA (2010) Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function. Am J Phys Regul Integr Comp Phys 298(3):R534–R547

    CAS  Google Scholar 

  89. 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(42):10847–10855

    Article  PubMed  CAS  Google Scholar 

  90. Pinto R, Frias B, Allen S, Dawbarn D, McMahon SB, Cruz F, Cruz CD (2010) Sequestration of brain derived nerve factor by intravenous delivery of TrkB-Ig2 reduces bladder overactivity and noxious input in animals with chronic cystitis. Neuroscience 166(3):907–916

    Article  PubMed  CAS  Google Scholar 

  91. DeBerry JJ, Saloman JL, Dragoo BK, Albers KM, Davis BM (2015) Artemin immunotherapy is effective in preventing and reversing cystitis-induced bladder hyperalgesia via TRPA1 regulation. J Pain 16(7):628–636

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Bespalov MM, Saarma M (2007) GDNF family receptor complexes are emerging drug targets. Trends Pharmacol Sci 28(2):68–74

    Article  PubMed  CAS  Google Scholar 

  93. Merighi A (2016) Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain. Expert Opin Ther Targets 20(2):193–208

    Article  PubMed  CAS  Google Scholar 

  94. Ikeda-Miyagawa Y, Kobayashi K, Yamanaka H, Okubo M, Wang S, Dai Y, Yagi H, Hirose M, Noguchi K (2015) Peripherally increased artemin is a key regulator of TRPA1/V1 expression in primary afferent neurons. Mol Pain 11:8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Lippoldt EK, Ongun S, Kusaka GK, McKemy DD (2016) Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRalpha3. Proc Natl Acad Sci U S A 113(16):4506–4511

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. 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(2):438–441 discussion 441-2

    Article  PubMed  CAS  Google Scholar 

  97. Guan NN, Nilsson KF, Wiklund PN, Gustafsson LE (2014) Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium. Biochim Biophys Acta 1840(12):3443–3451

    Article  PubMed  CAS  Google Scholar 

  98. Saban R, Undem BJ, Keith IM, Saban MR, Tengowski MW, Graziano FM, Bjorling DE (1994) Differential release of prostaglandins and leukotrienes by sensitized guinea pig urinary bladder layers upon antigen challenge. J Urol 152(2 Pt 1):544–549

    Article  PubMed  CAS  Google Scholar 

  99. 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(5):1951–1956

    Article  PubMed  CAS  Google Scholar 

  100. Gonzalez EJ, Arms L, Vizzard MA (2014) The role(s) of cytokines/chemokines in urinary bladder inflammation and dysfunction. Biomed Res Int 2014:120525

    PubMed  PubMed Central  Google Scholar 

  101. Hang L, Wullt B, Shen Z, Karpman D, Svanborg C (1998) Cytokine repertoire of epithelial cells lining the human urinary tract. J Urol 159(6):2185–2192

    Article  PubMed  CAS  Google Scholar 

  102. 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 Investig 77(1):37–49

    PubMed  CAS  Google Scholar 

  103. Nimmo AJ, Morrison JF, Whitaker EM (1988) A comparison of the distribution of substance P and calcitonin gene-related peptide receptors in the rat bladder. Q J Exp Physiol 73(5):789–792

    Article  PubMed  CAS  Google Scholar 

  104. Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313(5997):54–56

    Article  PubMed  CAS  Google Scholar 

  105. Miyoshi H, Nakaya Y (1995) Calcitonin gene-related peptide activates the K+ channels of vascular smooth muscle cells via adenylate cyclase. Basic Res Cardiol 90(4):332–336

    Article  PubMed  CAS  Google Scholar 

  106. Persson K, Garcia-Pascual A, Andersson KE (1991) Difference in the actions of calcitonin gene-related peptide on pig detrusor and vesical arterial smooth muscle. Acta Physiol Scand 143(1):45–53

    Article  PubMed  CAS  Google Scholar 

  107. Lu B, Figini M, Emanueli C, Geppetti P, Grady EF, Gerard NP, Ansell J, Payan DG, Gerard C, Bunnett N (1997) The control of microvascular permeability and blood pressure by neutral endopeptidase. Nat Med 3(8):904–907

    Article  PubMed  CAS  Google Scholar 

  108. Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A (1992) The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol 105(3):527–530

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Saban R (2015) Angiogenic factors, bladder neuroplasticity and interstitial cystitis-new pathobiological insights. Transl Androl Urol 4(5):555–562

    PubMed  PubMed Central  Google Scholar 

  110. Jaromi P, Garab D, Hartmann P, Bodnar D, Nyiri S, Santha P, Boros M, Jancso G, Szabo A (2017) Capsaicin-induced rapid neutrophil leukocyte activation in the rat urinary bladder microcirculatory bed. Neurourol Urodyn. https://doi.org/10.1002/nau.23376

  111. Kullmann F, Wolf-Johnston A, Bastacky S (2016) L. Birder, (377) Is pain a consequence of tissue remodeling in interstitial cystitis/bladder pain syndrome? J Pain 17(4S):S69

    Article  Google Scholar 

  112. Kiuchi H, Tsujimura A, Takao T, Yamamoto K, Nakayama J, Miyagawa Y, Nonomura N, Takeyama M, Okuyama A (2009) Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations. BJU Int 104(6):826–831 discussion 831

    Article  PubMed  Google Scholar 

  113. Saban R, Saban MR, Maier J, Fowler B, Tengowski M, Davis CA, Wu XR, Culkin DJ, Hauser P, Backer J, Hurst RE (2008) Urothelial expression of neuropilins and VEGF receptors in control and interstitial cystitis patients. Am J Physiol Ren Physiol 295(6):F1613–F1623

    Article  CAS  Google Scholar 

  114. Tamaki M, Saito R, Ogawa O, Yoshimura N, Ueda T (2004) Possible mechanisms inducing glomerulations in interstitial cystitis: relationship between endoscopic findings and expression of angiogenic growth factors. J Urol 172(3):945–948

    Article  PubMed  CAS  Google Scholar 

  115. Saban MR, Backer JM, Backer MV, Maier J, Fowler B, Davis CA, Simpson C, Wu XR, Birder L, Freeman MR, Soker S, Hurst RE, Saban R (2008) VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation. Am J Physiol Ren Physiol 295(1):F60–F72

    Article  CAS  Google Scholar 

  116. Ghassemifar R, Lai CM, Rakoczy PE (2006) VEGF differentially regulates transcription and translation of ZO-1alpha+ and ZO-1alpha- and mediates trans-epithelial resistance in cultured endothelial and epithelial cells. Cell Tissue Res 323(1):117–125

    Article  PubMed  CAS  Google Scholar 

  117. Saban MR, Davis CA, Avelino A, Cruz F, Maier J, Bjorling DE, Sferra TJ, Hurst RE, Saban R (2011) VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG. BMC Physiol 11:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Pang X, Boucher W, Triadafilopoulos G, Sant GR, Theoharides TC (1996) Mast cell and substance P-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis. Urology 47(3):436–438

    Article  PubMed  CAS  Google Scholar 

  119. Letourneau R, Pang X, Sant GR, Theoharides TC (1996) Intragranular activation of bladder mast cells and their association with nerve processes in interstitial cystitis. Br J Urol 77(1):41–54

    Article  PubMed  CAS  Google Scholar 

  120. Theoharides TC, Sant GR, el-Mansoury M, Letourneau R, Ucci AA Jr, Meares EM Jr (1995) Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. J Urol 153(3 Pt 1):629–636

    PubMed  CAS  Google Scholar 

  121. Letourneau R, Sant GR, el-Mansoury M, Theoharides TC (1992) Activation of bladder mast cells in interstitial cystitis. Int J Tissue React 14(6):307–312

    PubMed  CAS  Google Scholar 

  122. Theoharides TC, Kempuraj D, Sant GR (2001) Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology 57(6 Suppl 1):47–55

    Article  PubMed  CAS  Google Scholar 

  123. Sant GR, Kempuraj D, Marchand JE, Theoharides TC (2007) The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis. Urology 69(4 Suppl):34–40

    Article  PubMed  Google Scholar 

  124. Keith IM, Jin J, Saban R (1995) Nerve-mast cell interaction in normal guinea pig urinary bladder. J Comp Neurol 363(1):28–36

    Article  PubMed  CAS  Google Scholar 

  125. el-Mansoury M, Boucher W, Sant GR, Theoharides TC (1994) Increased urine histamine and methylhistamine in interstitial cystitis. J Urol 152(2 Pt 1):350–353

    Article  PubMed  CAS  Google Scholar 

  126. Saban R, D'Andrea MR, Andrade-Gordon P, Derian CK, Dozmorov I, Ihnat MA, Hurst RE, Davis CA, Simpson C, Saban MR (2007) Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation. BMC Physiol 7:4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. D'Andrea MR, Saban MR, Nguyen NB, Andrade-Gordon P, Saban R (2003) Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladder. Am J Pathol 162(3):907–923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, Brubaker L, Gai X, Wolfe AJ, Schreckenberger PC (2014) Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol 52:871–876

    Article  PubMed  PubMed Central  Google Scholar 

  129. Brubaker L, Wolfe AJ (2017) Microbiota in 2016: associating infection and incontinence with the female urinary microbiota. Nat Rev Urol 14(2):72–74

    Article  PubMed  PubMed Central  Google Scholar 

  130. Khasriya R, Sathiananthamoorthy S, Ismail S, Kelsey M, Wilson M, Rohn JL, Malone-Lee J (2013) Spectrum of bacterial colonization associated with urothelial cells from patients with chronic lower urinary tract symptoms. J Clin Microbiol 51(7):2054–2062

    Article  PubMed  PubMed Central  Google Scholar 

  131. Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, Wolfe AJ (2014) The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. MBio 5(4):e01283–e01214

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Pearce MM, Zilliox MJ, Rosenfeld AB, Thomas-White KJ, Richter HE, Nager CW, Visco AG, Nygaard IE, Barber MD, Schaffer J, Moalli P, Sung VW, Smith AL, Rogers R, Nolen TL, Wallace D, Meikle SF, Gai X, Wolfe AJ, Brubaker L, Pelvic Floor Disorders N (2015) The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol 213(3):347 e1–347 11

    Article  Google Scholar 

  133. Thomas-White KJ, Hilt EE, Fok C, Pearce MM, Mueller ER, Kliethermes S, Jacobs K, Zilliox MJ, Brincat C, Price TK, Kuffel G, Schreckenberger P, Gai X, Brubaker L, Wolfe AJ (2016) Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J 27(5):723–733

    Article  PubMed  Google Scholar 

  134. Schilling JD, Mulvey MA, Vincent CD, Lorenz RG, Hultgren SJ (2001) Bacterial invasion augments epithelial cytokine responses to Escherichia coli through a lipopolysaccharide-dependent mechanism. J Immunol 166:1148–1155

    Article  PubMed  CAS  Google Scholar 

  135. Thumbikat P, Berry RE, Zhou G, Billips BK, Yaggie RE, Zaichuk T, Sun TT, Schaeffer AJ, Klumpp DJ (2009) Bacteria-induced uroplakin signaling mediates bladder response to infection. PLoS Pathog 5:1–17

    Article  CAS  Google Scholar 

  136. Wood MW, Breitschwerdt EB, Nordone SK, Linder KE, Gookin JL (2011) Uropathogenic E. coli promote a paracellular urothelial barrier defect characterized by altered tight junction integrity, epithelial cell sloughing and cytokine release. J Comp Pathol 5:1–9

    Google Scholar 

  137. Birder LA, Klumpp DJ (2016) Host responses to urinary tract infections and emerging therapeutics: sensation and pain within the urinary tract. In: Mulvey MA, Stapleton AE, Klumpp DJ (eds) Microbiol spectrum. Northwestern University, Chicago

    Google Scholar 

  138. Abraham SN, Miao Y (2015) The nature of immune responses to urinary tract infections. Nat Rev Immunol 15:655–663

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Mo L (2004) Ablation of the Tamm-Horsfall protein gene increases susceptibility of mice to bladder colonization by type 1 fimbriated Eschericia coli. Am J Physiol Ren Physiol 286:F795–F802

    Article  CAS  Google Scholar 

  140. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB, Ganz T (1998) Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Rosen JM, Klumpp DJ (2014) Mechanisms of pain from urinary tract infection. Int J Urol 21:26–32

    Article  PubMed  PubMed Central  Google Scholar 

  142. Meseguer V, Alpizar YA, Luis E, Tajada S, Denlinger B, Fajardo O, Manenschijn JA, Fernandez-Pena C, Talavera A, Kichko T, Navia B, Sanchez A, Senaris R, Reeh P, Perez-Garcia MT, Lopez-Lopez JR, Voets T, Belmonte C, Talavera K, Viana F (2014) TRPA1 channels mediate acute neurogenic inflammation and pain produced by bacterial endotoxins. Nat Commun 5:3125

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Palea S, Corsi M, Artibani W, Ostardo E, Pietra C (1996) Pharmacological characterization of tachykinin NK2 receptors on isolated human urinary bladder, prostatic urethra and prostate. J Pharmacol Exp Ther 277(2):700–705

    PubMed  CAS  Google Scholar 

  144. Warner FJ, Miller RC, Burcher E (2003) Human tachykinin NK2 receptor: a comparative study of the colon and urinary bladder. Clin Exp Pharmacol Physiol 30(9):632–639

  145. Tramontana M, Patacchini R, Lecci A, Giuliani S, Maggi CA (1998) Tachykinin NK2 receptors in the hamster urinary bladder: in vitro and in vivo characterization. Naunyn Schmiedeberg's Arch Pharmacol 358(3):293–300

    Article  CAS  Google Scholar 

  146. Quinn T, Collins C, Baird AW (2004) Mechanisms of neurokinin A- and substance P-induced contractions in rat detrusor smooth muscle in vitro. BJU Int 94(4):651–657

    Article  PubMed  CAS  Google Scholar 

  147. Giuliani S, Patacchini R, Barbanti G, Turini D, Rovero P, Quartara L, Giachetti A, Maggi CA (1993) Characterization of the tachykinin neurokinin-2 receptor in the human urinary bladder by means of selective receptor antagonists and peptidase inhibitors. J Pharmacol Exp Ther 267(2):590–595

    PubMed  CAS  Google Scholar 

  148. Templeman L, Sellers DJ, Chapple CR, Rosario DJ, Hay DP, Chess-Williams R (2003) Investigation of neurokinin-2 and -3 receptors in the human and pig bladder. BJU Int 92(7):787–792

    Article  PubMed  CAS  Google Scholar 

  149. Maggi CA, Santicioli P, Giuliani S, Regoli D, Meli A (1986) Activation of micturition reflex by substance P and substance K: indirect evidence for the existence of multiple tachykinin receptors in the rat urinary bladder. J Pharmacol Exp Ther 238(1):259–266

    PubMed  CAS  Google Scholar 

  150. Maggi CA, Santicioli P, Geppetti P, Furio M, Frilli S, Conte B, Fanciullacci M, Giuliani S, Meli A (1987) The contribution of capsaicin-sensitive innervation to activation of the spinal vesico-vesical reflex in rats: relationship between substance P levels in the urinary bladder and the sensory-efferent function of capsaicin-sensitive sensory neurons. Brain Res 415(1):1–13

    Article  PubMed  CAS  Google Scholar 

  151. Kullmann FA, Kurihara R, Ye L, Wells GI, McKenna DG, Burgard EC, Thor KB (2013) Effects of the 5-HT4 receptor agonist, cisapride, on neuronally evoked responses in human bladder, urethra, and ileum. Auton Neurosci 176(1-2):70–77

    Article  PubMed  CAS  Google Scholar 

  152. Kullmann FA, Katofiasc M, Thor KB, Marson L (2017) Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4-10) prokinetic effects on bladder and colon activity in acute spinal cord transected and spinally intact rats. Naunyn Schmiedeberg's Arch Pharmacol 390(2):163–173

    Article  CAS  Google Scholar 

  153. Henderson L, Farrelly P, Dickson AP, Goyal A (2016) Management strategies for idiopathic urethritis. J Pediatr Urol 12(1):35 e1–35 e5

    Article  Google Scholar 

  154. Bachmann LH, Manhart LE, Martin DH, Sena AC, Dimitrakoff J, Jensen JS, Gaydos CA (2015) Advances in the understanding and treatment of male urethritis. Clin Infect Dis 61(Suppl 8):S763–S769

    Article  PubMed  Google Scholar 

  155. Tritschler S, Roosen A, Fullhase C, Stief CG, Rubben H (2013) Urethral stricture: etiology, investigation and treatments. Dtsch Arztebl Int 110(13):220–226

    PubMed  PubMed Central  Google Scholar 

  156. Ben-Meir D, Yin M, Chow CW, Hutson JM (2005) Urethral polyps in prepubertal girls. J Urol 174(4 Pt 1):1443–1444

    Article  PubMed  CAS  Google Scholar 

  157. Liedberg H (1989) Catheter induced urethral inflammatory reaction and urinary tract infection. An experimental and clinical study. Scand J Urol Nephrol Suppl 124:1–43

    PubMed  CAS  Google Scholar 

  158. Abelli L, Conte B, Somma V, Parlani M, Geppetti P, Maggi CA (1991) Mechanical irritation induces neurogenic inflammation in the rat urethra. J Urol 146(6):1624–1626

  159. Nordling L, Lundeberg T, Brolin J, Liedberg H, Ekman P, Theodorsson E (1992) The role of sensory nerves in catheter-induced urethral inflammation. Eur Urol 21(1):75–78

    Article  PubMed  CAS  Google Scholar 

  160. Nordling L, Liedberg H, Ekman P, Lundeberg T (1990) Influence of the nervous system on experimentally induced urethral inflammation. Neurosci Lett 115(2-3):183–188

    Article  PubMed  CAS  Google Scholar 

  161. Deckmann K, Filipski K, Krasteva-Christ G, Fronius M, Althaus M, Rafiq A, Papadakis T, Renno L, Jurastow I, Wessels L, Wolff M, Schutz B, Weihe E, Chubanov V, Gudermann T, Klein J, Bschleipfer T, Kummer W (2014) Bitter triggers acetylcholine release from polymodal urethral chemosensory cells and bladder reflexes. Proc Natl Acad Sci U S A 111(22):8287–8292

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Di Sant’Agnese PA, Davis NS, Chen M, de Mesy Jensen KL (1987) Age-related changes in the neuroendocrine (endocrine-paracrine) cell population and the serotonin content of the guinea pig prostate. Lab Investig 57(6):729–736

    PubMed  Google Scholar 

  163. di Sant’Agnese PA, de Mesy Jensen KL (1987) Endocrine-paracrine (APUD) cells of the human female urethra and paraurethral ducts. J Urol 137(6):1250–1254

    Article  PubMed  Google Scholar 

  164. Hakanson R, Larsson LI, Sjoberg NO, Sundler F (1974) Amine-producing endocrine-like cells in the epithelium of urethra and prostate of the guinea-pig. A chemical, fluorescence histochemical, and electron microscopic study. Histochemie 38(3):259–270

    Article  PubMed  CAS  Google Scholar 

  165. Hanyu S, Iwanaga T, Kano K, Fujita T (1987) Distribution of serotonin-immunoreactive paraneurons in the lower urinary tract of dogs. Am J Anat 180(4):349–356

    Article  PubMed  CAS  Google Scholar 

  166. Iwanaga T, Han H, Hoshi O, Kanazawa H, Adachi I, Fujita T (1994) Topographical relation between serotonin-containing paraneurons and peptidergic neurons in the intestine and urethra. Biol Signals 3(5):259–270

    Article  PubMed  CAS  Google Scholar 

  167. Iwanaga T, Hanyu S, Fujita T (1987) Serotonin-immunoreactive cells of peculiar shape in the urethral epithelium of the human penis. Cell Tissue Res 249(1):51–56

    Article  PubMed  CAS  Google Scholar 

  168. Vittoria A, La Mura E, Cocca T, Cecio A (1990) Serotonin-, somatostatin- and chromogranin A-containing cells of the urethro-prostatic complex in the sheep. An immunocytochemical and immunofluorescent study. J Anat 171:169–178

    PubMed  PubMed Central  CAS  Google Scholar 

  169. Yokoyama T, Saino T, Nakamuta N, Yamamoto Y (2017) Topographic distribution of serotonin-immunoreactive urethral endocrine cells and their relationship with calcitonin gene-related peptide-immunoreactive nerves in male rats. Acta Histochem 119(1):78–83

    Article  PubMed  CAS  Google Scholar 

  170. Kummer W, Deckmann K (2017) Brush cells, the newly identified gatekeepers of the urinary tract. Curr Opin Urol 27(2):85–92

    Article  PubMed  Google Scholar 

  171. Deckmann K, Kummer W (2016) Chemosensory epithelial cells in the urethra: sentinels of the urinary tract. Histochem Cell Biol 146(6):673–683

    Article  PubMed  CAS  Google Scholar 

  172. Everaerts W, Gevaert T, Nilius B, De Ridder D (2008) On the origin of bladder sensing: Tr(i)ps in urology. Neurourol Urodyn 27(4):264–273

    Article  PubMed  CAS  Google Scholar 

  173. Andersson KE, Gratzke C, Hedlund P (2010) The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int 106(8):1114–1127

    Article  PubMed  CAS  Google Scholar 

  174. 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(1):34–38

    Article  PubMed  CAS  Google Scholar 

  175. 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(2):575–579

    Article  PubMed  CAS  Google Scholar 

  176. 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(4):650–655

    Article  PubMed  CAS  Google Scholar 

  177. 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(3):947–952

    Article  PubMed  CAS  Google Scholar 

  178. Foster HE Jr, Lake AG (2014) Use of vanilloids in urologic disorders. Prog Drug Res 68:307–317

    PubMed  CAS  Google Scholar 

  179. Palea S, Guilloteau V, Rekik M, Lovati E, Guerard M, Guardia MA, Lluel P, Pietra C, Yoshiyama M (2016) Netupitant, a potent and highly selective NK1 receptor antagonist, alleviates acetic acid-induced bladder overactivity in anesthetized guinea-pigs. Front Pharmacol 7:234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Frenkl TL, Zhu H, Reiss T, Seltzer O, Rosenberg E, Green S (2010) A multicenter, double-blind, randomized, placebo controlled trial of a neurokinin-1 receptor antagonist for overactive bladder. J Urol 184(2):616–622

    Article  PubMed  CAS  Google Scholar 

  181. Green SA, Alon A, Ianus J, McNaughton KS, Tozzi CA, Reiss TF (2006) Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence. J Urol 176(6 Pt 1):2535–2540 discussion 2540

    Article  PubMed  CAS  Google Scholar 

  182. Haab F, Braticevici B, Krivoborodov G, Palmas M, Zufferli Russo M, Pietra C (2014) Efficacy and safety of repeated dosing of netupitant, a neurokinin-1 receptor antagonist, in treating overactive bladder. Neurourol Urodyn 33(3):335–340

    Article  PubMed  CAS  Google Scholar 

  183. Ford AP, Undem BJ (2013) The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front Cell Neurosci 7:267

    PubMed  PubMed Central  Google Scholar 

  184. Moldwin R, Kitt M, Mangel J, Beyer R, Hanno P, Butera P, Ford A (2015) A phase 2 study in women with interstitial cystitis/bladder pain syndrome (IC/BPS) of the novel P2X3 antagonist AF-219, International Contionence. Society

  185. Ikeda Y, Zabbarova I, Lemon K, Lamarre N, Epperly M, Kanai A (2015) Treatment of radiation cystitis via P75 receptor blockade. J Urol 193(4):e237

  186. Nickel JC, Atkinson G, Krieger JN, Mills IW, Pontari M, Shoskes DA, Crook TJ (2012) Preliminary assessment of safety and efficacy in proof-of-concept, randomized clinical trial of tanezumab for chronic prostatitis/chronic pelvic pain syndrome. Urology 80(5):1105–1110

    Article  PubMed  Google Scholar 

  187. Nickel JC, Mills IW, Crook TJ, Jorga A, Smith MD, Atkinson G, Krieger JN (2016) Tanezumab reduces pain in women with interstitial cystitis/bladder pain syndrome and patients with nonurological associated somatic syndromes. J Urol 195(4 Pt 1):942–948

    Article  PubMed  CAS  Google Scholar 

  188. Evans RJ, Moldwin RM, Cossons N, Darekar A, Mills IW, Scholfield D (2011) Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J Urol 185(5):1716–1721

    Article  PubMed  CAS  Google Scholar 

  189. Peng CH, Jhang JF, Shie JH, Kuo HC (2013) Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical OnabotulinumtoxinA injections combined with hydrodistention for patients with interstitial cystitis—clinical results and immunohistochemistry analysis. Urology 82(6):1452 e1–1452 e6

    Article  Google Scholar 

  190. Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE (2008) Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int 101(3):366–370

    Article  PubMed  CAS  Google Scholar 

  191. 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(4 Pt 1):1529–1532

    Article  PubMed  CAS  Google Scholar 

  192. 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(2):786–792

    Article  PubMed  CAS  Google Scholar 

  193. Rapp DE, Turk KW, Bales GT, Cook SP (2006) Botulinum toxin type a inhibits calcitonin gene-related peptide release from isolated rat bladder. J Urol 175(3 Pt 1):1138–1142

    Article  PubMed  CAS  Google Scholar 

  194. Hanna-Mitchell AT, Wolf-Johnston AS, Barrick SR, Kanai AJ, Chancellor MB, de Groat WC, Birder LA (2015) Effect of botulinum toxin A on urothelial-release of ATP and expression of SNARE targets within the urothelium. Neurourol Urodyn 34(1):79–84

    Article  PubMed  CAS  Google Scholar 

  195. Smith CP, Radziszewski P, Borkowski A, Somogyi GT, Boone TB, Chancellor MB (2004) Botulinum toxin a has antinociceptive effects in treating interstitial cystitis. Urology 64(5):871–875 discussion 875

    Article  PubMed  Google Scholar 

  196. Kuo HC, Jiang YH, Tsai YC, Kuo YC (2016) Intravesical botulinum toxin-A injections reduce bladder pain of interstitial cystitis/bladder pain syndrome refractory to conventional treatment—a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial. Neurourol Urodyn 35(5):609–614

    Article  PubMed  CAS  Google Scholar 

  197. Shie JH, Liu HT, Wang YS, Kuo HC (2013) Immunohistochemical evidence suggests repeated intravesical application of botulinum toxin A injections may improve treatment efficacy of interstitial cystitis/bladder pain syndrome. BJU Int 111(4):638–646

    Article  PubMed  CAS  Google Scholar 

  198. Jhang JF, Kuo HC (2016) Botulinum toxin A and lower urinary tract dysfunction: Pathophysiology and mechanisms of action. Toxins (Basel) 8(4):120

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Institute of Health through the following grants: R37 DK54824 to LAB and P30 DK079307 Pittsburgh Center for Kidney Research–O’Brien Pilot to FAK. The authors also thank Dr. Bronagh McDonnell for critical reading of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lori A. Birder.

Additional information

This article is a contribution to the special issue on Neurogenic Inflammation - Guest Editors: Tony Yaksh and Anna Di Nardo

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Birder, L.A., Kullmann, F.A. Role of neurogenic inflammation in local communication in the visceral mucosa. Semin Immunopathol 40, 261–279 (2018). https://doi.org/10.1007/s00281-018-0674-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-018-0674-0

Keywords

Navigation