International Urogynecology Journal

, Volume 25, Issue 11, pp 1561–1567 | Cite as

Urinary nerve growth factor correlates with the severity of urgency and pain

  • Sang Woon Kim
  • Young Jae Im
  • Ho Chul Choi
  • Hyo Jin Kang
  • Ji Yu Kim
  • Jang Hwan Kim
Original Article

Abstract

Introduction and hypothesis

Urinary nerve-growth-factor (NGF) level reflected the severity of urgency in patients with lower urinary tract symptoms (LUTS) and pain in patients with Bladder pain syndrome/interstitial cystitis (BPS/IC). The aim of this study was to investigate the levels of biomarkers, nerve growth factor (NGF), and prostaglandin E2 (PGE2) among disease groups sharing similar urinary symptoms and to elucidate which symptoms are related to individual biomarker levels.

Methods

We studied 83 patients with LUTS who visited our outpatient clinic from May 2011 to December 2012. On the basis of clinical symptoms and a 3-day voiding diary, patients were classified into three groups: those with frequency (n = 13), overactive bladder (OAB) (n = 35), and BPS/IC (n = 35). Patients with stress urinary incontinence (SUI) or microscopic hematuria served as controls (n = 24). Storage symptoms were evaluated based on OAB symptom score (OAB-SS).

Results

Mean patient age was 62.08 ± 11.47 (range, 23–84). Urinary NGF and creatinine-normalized NGF levels were significantly increased in those with OAB (201.90 and 4.08, respectively) and BPS/IC (173.71 and 2.72) compared with controls (77.77 and 1.29) and those with frequency (67.76 and 1.23). Neither value significantly differed between OAB and BPS/IC patients or between controls and frequency patients. Urinary PGE2 and creatinine-normalized PGE2 levels were not significantly different among groups. On linear regression analysis, urinary NGF levels were significantly correlated with urgency severity overall (R = 0.222) and also pain in BPS/IC patients (R = 0.409).

Conclusions

The levels of urinary NGF were elevated in patients with OAB and BPS/IC but not those with frequency and reflected the severity of urgency. In BPS/IC patients, urinary NGF increased with pain severity.

Keywords

Nerve growth factor Overactive bladder PGE2 Urge incontinence 

Abbreviations & Acronyms

NGF

Nerve growth factor

PGE2

Prostaglandin E2

LUTS

Lower urinary tract symptoms

OAB

Overactive bladder

OAB-SS

Overactive Bladder Symptom Score

BPS/IC

Bladder pain syndrome/interstitial cystitis

TRPV

Transient receptor potential vanilloid

TRPM8

Transient receptor potential melastatin type 8

UI

Urinary incontinence

Notes

Acknowledgments

This study was supported by a faculty research grant of Yonsei University College of Medicine for 2011 (6-2011-0109).

Conflict of interest

None.

References

  1. 1.
    International Urogynecological A, International Continence S, Haylen BT, de Ridder D, Freeman RM, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk DE, Sand PK, Schaer GN (2010) An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn 29(1):4–20. doi:10.1002/nau.20798 PubMedGoogle Scholar
  2. 2.
    Liu HT, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol 56(4):700–706. doi:10.1016/j.eururo.2008.04.037 PubMedCrossRefGoogle Scholar
  3. 3.
    Liu HT, Chancellor MB, Kuo HC (2009) Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder. BJU Int 103(12):1668–1672. doi:10.1111/j.1464-410X.2009.08380.x PubMedCrossRefGoogle Scholar
  4. 4.
    Steers WD, Kolbeck S, Creedon D, Tuttle JB (1991) Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest 88(5):1709–1715. doi:10.1172/JCI115488 PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    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(3):975–979PubMedCrossRefGoogle Scholar
  6. 6.
    Antunes-Lopes T, Pinto R, Barros SC, Botelho F, Silva CM, Cruz CD, Cruz F (2013) Urinary neurotrophic factors in healthy individuals and patients with overactive bladder. J Urol 189(1):359–365. doi:10.1016/j.juro.2012.08.187 PubMedCrossRefGoogle Scholar
  7. 7.
    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. doi:10.1371/journal.pone.0044687 PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Kim JC, Park EY, Seo SI, Park YH, Hwang TK (2006) Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 175(5):1773–1776. doi:10.1016/S0022-5347(05)00992-4, discussion 1776PubMedCrossRefGoogle Scholar
  9. 9.
    van de Merwe JP, Nordling J, Bouchelouche P, Bouchelouche K, Cervigni M, Daha LK, Elneil S, Fall M, Hohlbrugger G, Irwin P, Mortensen S, van Ophoven A, Osborne JL, Peeker R, Richter B, Riedl C, Sairanen J, Tinzl M, Wyndaele JJ (2008) Diagnostic criteria, classification, and nomenclature for painful bladder syndrome/interstitial cystitis: an ESSIC proposal. Eur Urol 53(1):60–67. doi:10.1016/j.eururo.2007.09.019 PubMedCrossRefGoogle Scholar
  10. 10.
    Homma Y (2013) Hypersensitive bladder: towards clear taxonomy surrounding interstitial cystitis. Int J Urol Off J Jpn Urol Assoc 20(8):742–743. doi:10.1111/iju.12143 Google Scholar
  11. 11.
    Homma Y, Yoshida M, Seki N, Yokoyama O, Kakizaki H, Gotoh M, Yamanishi T, Yamaguchi O, Takeda M, Nishizawa O (2006) Symptom assessment tool for overactive bladder syndrome–overactive bladder symptom score. Urology 68(2):318–323. doi:10.1016/j.urology.2006.02.042 PubMedCrossRefGoogle Scholar
  12. 12.
    Liu HT, Chen CY, Kuo HC (2011) Urinary nerve growth factor in women with overactive bladder syndrome. BJU Int 107(5):799–803. doi:10.1111/j.1464-410X.2010.09585.x PubMedCrossRefGoogle Scholar
  13. 13.
    Liu HT, Tyagi P, Chancellor MB, Kuo HC (2010) Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity. BJU Int 106(11):1681–1685. doi:10.1111/j.1464-410X.2009.08851.x PubMedCrossRefGoogle Scholar
  14. 14.
    Frias B, Charrua A, Avelino A, Michel MC, Cruz F, Cruz CD (2012) Transient receptor potential vanilloid 1 mediates nerve growth factor-induced bladder hyperactivity and noxious input. BJU Int 110(8 Pt B):E422–E428. doi:10.1111/j.1464-410X.2012.11187.x PubMedCrossRefGoogle Scholar
  15. 15.
    Girard BM, Merrill L, Malley S, Vizzard MA (2013) Increased TRPV4 expression in urinary bladder and lumbosacral dorsal root ganglia in mice with chronic overexpression of NGF in urothelium. J Mol Neurosci MN 51(2):602–614. doi:10.1007/s12031-013-0033-5 CrossRefGoogle Scholar
  16. 16.
    Skryma R, Prevarskaya N, Gkika D, Shuba Y (2011) From urgency to frequency: facts and controversies of TRPs in the lower urinary tract. Nat Rev Urol 8(11):617–630. doi:10.1038/nrurol.2011.142 PubMedCrossRefGoogle Scholar
  17. 17.
    Liu HT, Tyagi P, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int 104(10):1476–1481. doi:10.1111/j.1464-410X.2009.08675.x PubMedCrossRefGoogle Scholar
  18. 18.
    Vizzard MA (2000) Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol 161(1):273–284. doi:10.1006/exnr.1999.7254 PubMedCrossRefGoogle Scholar
  19. 19.
    Mukerji G, Yiangou Y, Corcoran SL, Selmer IS, Smith GD, Benham CD, Bountra C, Agarwal SK, Anand P (2006) Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 6:6. doi:10.1186/1471-2490-6-6 PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Luo W, Wickramasinghe SR, Savitt JM, Griffin JW, Dawson TM, Ginty DD (2007) A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons. Neuron 54(5):739–754. doi:10.1016/j.neuron.2007.04.027 PubMedCrossRefGoogle Scholar
  21. 21.
    McCafferty GP, Misajet BA, Laping NJ, Edwards RM, Thorneloe KS (2008) Enhanced bladder capacity and reduced prostaglandin E2-mediated bladder hyperactivity in EP3 receptor knockout mice. Am J Physiol Renal Physiol 295(2):F507–F514. doi:10.1152/ajprenal.00054.2008 PubMedCrossRefGoogle Scholar
  22. 22.
    Ishizuka O, Mattiasson A, Andersson KE (1995) Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins? J Urol 153(6):2034–2038PubMedCrossRefGoogle Scholar
  23. 23.
    Schussler B (1990) Comparison of the mode of action of prostaglandin E2 (PGE2) and sulprostone, a PGE2-derivative, on the lower urinary tract in healthy women. A urodynamic study. Urol Res 18(5):349–352PubMedCrossRefGoogle Scholar
  24. 24.
    Clemow DB, Steers WD, Tuttle JB (2000) Stretch-activated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats. J Cell Physiol 183(3):289–300. doi:10.1002/(SICI)1097-4652(200006)183:3<289::AID-JCP1>3.0.CO;2-6 PubMedCrossRefGoogle Scholar
  25. 25.
    Kuo HC, Liu HT, Chancellor MB (2010) Urinary nerve growth factor is a better biomarker than detrusor wall thickness for the assessment of overactive bladder with incontinence. Neurourol Urodyn 29(3):482–487. doi:10.1002/nau.20741 PubMedGoogle Scholar

Copyright information

© The International Urogynecological Association 2014

Authors and Affiliations

  • Sang Woon Kim
    • 1
  • Young Jae Im
    • 1
  • Ho Chul Choi
    • 1
  • Hyo Jin Kang
    • 1
  • Ji Yu Kim
    • 1
  • Jang Hwan Kim
    • 1
  1. 1.Department of Urology, Urological Science InstituteYonsei University College of MedicineSeodaemun-guSouth Korea

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