Urothelial dysfunction and sensory protein expressions in ketamine cystitis – comparision with interstitial cystitis
Jia-Fong Jhang, Hann-Chorng Kuo
Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
Purpose: Ketamine related cystitis (KC) is a newly developed clinical syndrome, and it has many similar characteristics with interstitial cystitis (IC), such as bladder pain and urinayr frequency. Previous animal study suggested urothelial dysfunction and abnormal sensory protein expression might participate the pathogenesis of IC . Current study is designed to investigate the urothelial function and protein expression in human KC bladder and compare with IC bladder.
Materials and Methods: The KC and IC patients who were admitted to our hospital for cystoscopic hydrodistention were enrolled into this study. Tirty bladder random cold cup biopsies from KC bladder and thirty-two bladder specimen for IC bladder were taken during cystoscopic hydrodistention, and the specimens were investigated for E-cadherin, zona occludens 1 (ZO-1), tryptase, and TUNEL with immunofluorescence staining and quantification. Specimens obtained were investigated for muscarinic receptors M2, M3, TGF-beta, β3, eNOS and P2X3 with Western blotting. Ten healthy control bladder specimens were also investigated and compared with KC bladder. The symptoms, duration of ketamine abuse and urodynamics examination parameters in the KC patients were also analyzed.
Results: The KC bladder specimens showed significantly lower expression of E-cadherin and ZO-1, and higher expression of TUNEL and tryptase activity than the control bladder specimens. M3 expression in KC bladder was also significantly increased than that in control subjectives. The expression of M2, e-NOS, P2X3 and TGF- beta did not have difference between KC bladder and control. The ketamine abuse history, visual analogue scale pain score, cystometric bladder capacity and maximal bladder capacity under anesthesia did not have significant correlation with M2, M3, e-NOS and P2X3. When compared to IC bladder specimen, the KC specimen had significantly lower M2 and e-NOS expression. The β3 is significantly higher in KC than that in IC bladder. The E-cadherin, ZO-1, tryptase, TUNEL, M3 and P2X3 expression had no significant diffierence between KC and IC specimen.
Conclusions: KC bladder tissue showed urothelial dysfunction, mast cell mediated inflammation, increased apoptosis and increased muscarinic receptors. These finding might participate the pathogenesis of KC. The difference sensory and inflammatory protein between IC and KC might imply different pathogenesis in the two disease.