Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 2, February, p. 159–163

doi: 10.17219/acem/69231

Publication type: original article

Language: English

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Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis

Senol Tonyali1,A,B,C,D,E,F, Deniz Ates2,A,B,C,D,E,F, Filiz Akbiyik3,A,B,C,D,E,F, Duygu Kankaya4,A,B,C,D,E,F, Dilek Baydar2,A,B,C,D,E,F, Ali Ergen1,A,B,C,D,E,F

1 Department of Urology, Hacettepe University School of Medicine, Ankara, Turkey

2 Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey

3 Department of Medical Biochemistry, Hacettepe University School of Medicine, Ankara, Turkey

4 Department of Pathology, Ankara University School of Medicine, Ankara, Turkey

Abstract

Background. Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a challenging disease, affecting thousands of people all around the world, especially women. Although there have been numerous theories regarding IC/BPS etiology, the physiopathology of the disease still remains unclear and there is a lack of certain treatment.
Objectives. The aim of the study was to assess the role of nerve fibers and nerve growth factor (NGF) in the etiopathogenesis of IC/BPS symptoms by demonstrating if there is a correlation between urine NGF levels, amount of peripheral nerves in bladder mucosa and symptom severity.
Material and Methods. A prospective clinical study was conducted with 15 IC/BPS patients and 18 controls. Urine NGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Bladder punch biopsies were obtained from 15 IC/BPS patients and 9 controls. Immunohistochemistry was performed for S-100 to highlight peripheral nerve twigs in bladder mucosa. The O’Leary-Sant Interstitial Cystitis Symptom and Problem Index (OSICSPI) was used to assess symptom severity and effects of the disease on the patients’ life.
Results. NGF normalized to urine creatinine (NGF/Cr) levels in IC/BPS patients were significantly higher than in controls, 0.34 ±0.22 and 0.09 ±0.08 pg/mL: mg/dL, respectively (p < 0.001). The mean symptom score in IC patients was 12.27 ±2.4 (median: 12) and the mean problem score was 10.9 ±2.3 (median: 12). The mean mucosal nerve (S-100 stained) area in the IC/BPS group was significantly higher than in the controls, 2.53 ±1.90 vs 1.0 ±0.70, respectively (p = 0.018). In correlation analyses, the NGF/Cr level in IC/BPS patients was found significantly correlated with the O’Leary-Sant IC Symptom and Problem Index scores independently (p = 0.001 and p = 0.028, respectively).
Conclusion. NGF seems to be a promising biomarker in IC/BPS. It may help clinicians in diagnoses and patient follow-up. Thus, unnecessary, expensive and invasive tests, interventions and treatments might be avoided.

Key words

nerve growth factor, bladder pain syndrome/interstitial cystitis, nerve staining

References (24)

  1. Hanno PM, Burks DA, Clemens JQ, et al. AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2011;185;2162–2170.
  2. Chennamsetty A, Ehlert MJ, Peters KM, Killinger KA. Advances in diagnosis and treatment of interstitial cystitis/painful bladder syndrome. Curr Infect Dis Rep. 2015;17:454.
  3. Qu HC, Zhang W, Yan S, Liu YL, Wang P. Urinary nerve growth factor could be a biomarker for interstitial cystitis/painful bladder syndrome: A meta-analysis. PLoS One. 2014;9:e106321.
  4. O’Leary MP, Sant GR, Fowler FJ Jr, Whitmore KE, Spolarich-Kroll J. The interstitial cystitis symptom index and problem index. Urology. 1997;49:58–63.
  5. Hanno P, Lin A, Nordling J, et al. Bladder Pain Syndrome Committee of the International Consultation on Incontinence. Neurourol Urodyn. 2010;29:191–198.
  6. Davis NF, Brady CM, Creagh T. Interstitial cystitis/painful bladder syndrome: Epidemiology, pathophysiology and evidence-based treatment options. Eur J Obstet Gynecol Reprod Biol. 2014;175:30–37.
  7. Warren JW. Bladder pain syndrome/interstitial cystitis as a functional somatic syndrome. J Psychosom Res. 2014;77:510–515.
  8. Keay SK, Zhang CO, Shoenfelt J, et al. Sensitivity and specificity of antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor as urine markers for interstitial cystitis. Urology. 2001;57:9–14.
  9. Malykhina AP. Neural mechanisms of pelvic organ cross-sensitization. Neuroscience. 2007;149:660–672.
  10. Sant GR, Kempuraj D, Marchand JE, Theoharides TC. The mast cell in interstitial cystitis: Role in pathophysiology and pathogenesis. Urology. 2007;69:34–40.
  11. Warren JW. Is interstitial cystitis an infectious disease? Med Hypotheses. 1994;43:183–186.
  12. Hand JR. Interstitial cystitis: Report of 223 cases (204 women and 19 men). J Urol. 1949;61:291–310.
  13. Christmas TJ, Rode J, Chapple CR, Milroy EJ, Turner-Warwick RT. Nerve fibre proliferation in interstitial cystitis. Virchows Arch A Pathol Anat Histopathol. 1990;416:447–451.
  14. Pang X, Marchand J, Sant GR, Kream RM, Theoharides TC. Increased number of substance P positive nerve fibres in interstitial cystitis. 1995;75:744–750.
  15. Hofmeister MA, He F, Ratliff TL, Mahoney T, Becich MJ. Mast cells and nerve fibers in interstitial cystitis (IC): An algorithm for histologic diagnosis via quantitative image analysis and morphometry (QIAM). Urology. 1997;49:41–47.
  16. Lowe EM, Anand P, Terenghi G, Williams-Chestnut RE, Sinicropi DV, Osborne JL. Increased nerve growth factor levels in the urinary bladder of women with idiopathic sensory urgency and interstitial cystitis. Br J Urol. 1997;79:572–577.
  17. Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007;70:463–468.
  18. Liu HT, Tyagi P, Chancellor MB, Kuo HC. Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment. BJU Int. 2009; 104:1476–1481.
  19. Jacobs BL, Smaldone MC, Tyagi V, et al. Increased nerve growth factor in neurogenic overactive bladder and interstitial cystitis patients. Can J Urol. 2010;17:4989–4994.
  20. Liu HT, Kuo HC. Increased urine and serum nerve growth factor levels in interstitial cystitis suggest chronic inflammation is involved in the pathogenesis of disease. PLoS One. 2012;7:e44687.
  21. Liu BL, Yang F, Zhan HL, et al. Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome. Urol Int. 2014;92:202–208.
  22. Nickel JC, Mills IW, Crook TJ, et al. Tanezumab reduces pain in women with interstitial cystitis/bladder pain syndrome and patients with nonurological associated somatic syndromes. J Urol. 2016;195:942–948.
  23. Evans RJ, Moldwin RM, Cossons N, Darekar A, Mills IW, Scholfield D. Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J Urol. 2011;185:1716–1721.
  24. Sofroniew MV, Howe CL, Mobley WC. Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci. 2001;24:1217–1281.
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