張嘉峰、郭漢崇

花蓮慈濟醫院 泌尿部

Jia-Fong Jhang, Hann-Chorng Kuo

Department of Urology, Haulien Tzu Chi Hospital.

 

Purpose: Previous studies showed the symptoms aggravation with stress in the patients with interstitial cystitis/bladder pain syndrome (IC/BPDS). Sensory hyperinnervation was also found in the IC/BPS bladder. However, the pathogenesis pathway was still unclear. The aim of current study is to investigate the stress associated receptors and neurotrophin expression in the urothelium of IC/BPS patients

Materials and Methods: The patients with IC/BPS who were admitted to our hospital for cystoscopic hydrodistention were recruited into this study. These patients were classified into ulcer and non-ulcer IC/BPS according to the cystoscopic finding of Hunner’s lesion. Random cold-cup biopsies of the posterior bladder wall in these patients were obtained after cystoscopic hydrodistention.  Western blotting with quantification was used to investigate the expression of neurotrophin growth associated protein 43 (GAP-43), nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TrkA) in these bladder specimens. The stress associated receptor, corticotropin releasing factor receptor (CRFR) 1 and 2, were also investigated with western blotting. Fluorescent immunochemical staining was also performed to verify the location of CRFR1 expression in the urothelium. Bladder specimens from female patients with stress urinary incontinence were also obtained for western blotting and were considered as normal control. Pearson’s correlation coefficients were calculated to determine the correlations between the quantification results of western blotting and clinical symptoms scores, including Interstitial Cystitis Symptoms and Problem Index (ICSI and ICPI), Visual Analogue Scale for pain (VAS).

Results: A total of 62 IC/BPS patients (23 ulcer IC/BPS and 39 non-ulcer IC/BPS) and 24 normal controls were enrolled. The patients with non-ulcer IC/BPS were younger than ulcer IC/BPS and controls. Among 3 groups, the western blotting revealed the urothelium in the ulcer IC/BPS had significantly higher expression NGF, Trk-A and CRFR1. The urothelium CRFR2 also significantly decreased in the ulcer IC/BPS. The GAP-43 expression was significantly lower in the non-ulcer IC/BPS. Among all IC/BPS patients, the CRFR2 expression was significantly negative correlated with ICSI, ICPI and VAS (r=-0.362.-0.439, -0.372; p-value= 0.017, 0.003, 0.014, respectively). The NGF expression in the urothelium was significantly correlated with the maximal bladder capacity, cystometric bladder capacity and CRFR1 (r=-0.272, -0.310 and 0.482; p=0.034, 0.028, 0.001, respectively). The immunochemical staining also revealed CRFR1 expression in the cell membrane of in the urothelium of IC/BPS patients.

Conclusions: Neurotrophin and stress associated receptors expression levels were significantly increased in the ulcer IC/BPS patients, and were significantly correlated with clinical symptoms. Neurotrophin and stress associated receptors may play an important role of in the pathogenesis of IC/BPS.