scholarly journals Differential expression of histamine receptors in the bladder wall tissues of patients with bladder pain syndrome/interstitial cystitis – significance in the responsiveness to antihistamine treatment and disease symptoms

BMC Urology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hui Shan ◽  
Er-Wei Zhang ◽  
Peng Zhang ◽  
Xiao-Dong Zhang ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Western Blotting ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Histamine Receptors ◽  
Receptor Expression ◽  
Bladder Pain ◽  
Disease Symptoms ◽  
Female Patients

Abstract Background Activation of mast cells plays an important role in the pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC). Histamine, a mast cell-derived mediators, induced inflammation and hypersensitivity of the bladder. The present study investigated the expressions of histamine receptors in the bladder wall tissues of patients with BPS/IC, and its association with the effectiveness of antihistamine therapy and disease symptoms. Methods Bladder tissues were collected from 69 BPS/IC patients and 10 control female patients. The expression of H3R in BPS/IC was further examined in an independent cohort of 10 female patients with BPS/IC and another 10 age-matched female patients. Immunohistochemistry, Western blotting, and quantitative RT-PCR were performed to quantify the expressions of histamine receptors. Statistical analyses of the correlation of histamine receptor expression with antihistamine therapy outcome and severity of disease symptoms were also performed. Results The expression of four histamine receptors was significantly elevated in BPS/IC (H1R, P < 0.001; H2R, P = 0.031; H3R, P = 0.008; H4R, P = 0.048). Western blotting revealed that H3R were significantly reduced in the patients, whereas the mRNA levels of H3R were significantly increased. The patients were further divided into antihistamine responders (n = 38) and nonresponders (n = 22). No significant correlation was found in the expression of histamine receptors between responder and nonresponder groups. However, significant correlations between OLS and H1R (P = 0.003) and H3R (P = 0.045) were found. Conclusion The present study showed that expression of all the 4 histamine receptors were elevated in BPS/IC. There were no statistical significant correlations between the expression levels of the four different histamine receptors and the treatment outcome of antihistamine therapy (amtitriptyline or cimetidine).

scholarly journals Dysregulation of bladder corticotropin-releasing hormone receptor in the pathogenesis of human interstitial cystitis/bladder pain syndrome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jia-Fong Jhang ◽  
Lori A. Birder ◽  
Yuan-Hong Jiang ◽  
Yung-Hsiang Hsu ◽  
Han-Chen Ho ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Hormone Receptor ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Corticotropin Releasing Hormone ◽  
Bladder Pain ◽  
Releasing Hormone ◽  
Control Subjects ◽  
And Control

AbstractStress is associated with exacerbated symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). To investigate the mechanism of stress implicated on IC/BPS, we investigated expression of stress-response receptor corticotropin-releasing hormone receptor (CRHR) in bladder from IC/BPS patients. Twenty-three IC/BPS patients with Hunner’s lesion (HIC), 51 IC/BPS patients without Hunner’s lesion (NHIC), and 24 patients with stress urinary incontinence as controls were enrolled. Cystoscopic biopsies of bladder wall including mucosa and submucosa were obtained from all patients. Western blotting was used to investigate the bladder expression of the CRHR1 and CRHR2. Immunochemical staining revealed CRHR1 expression was mainly located in the submucosa while CRHR2 expression was mainly in uroepithelial cells. Compared to control subjects, the CRHR1 expression was significantly higher, while CRHR2 expression was significantly lower in IC/BPS patients. Further analysis of patients with HIC, NHIC, and control subjects showed that bladder in patients with HIC had significantly higher expressions of CRHR1 and significantly lower CRHR2. CRHR2 expression was significantly negatively correlated with O’Leary-Sant score and bladder pain. Our results indicate dysregulation of bladder CRHR1 and CRHR2 in patients with IC/BPS, and suggest CRH signaling may be associated with IC/BPS symptoms.

Clinical and histological findings in bladder pain syndrome/interstitial cystitis: The implication of time of symptoms

2018 ◽  
Vol 11 (4) ◽  
pp. 248-253
Author(s):  
Daniele Porru ◽  
Valentina Bobbi ◽  
Carmelo Di Franco ◽  
Alessandra Viglio ◽  
Mattia Novario ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Symptom Onset ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Detrusor Muscle ◽  
Level Of Evidence ◽  
Bladder Pain ◽  
Bladder Biopsy ◽  
The Impact

Objective: To find out whether a correlation exists between denudation of urothelium and time of symptom onset in patients with bladder pain syndrome/interstitial cystitis (BPS/IC), and to search for a correlation between the impact of symptoms. Patients and methods: Fifty-seven consecutive patients underwent cystoscopy under anaesthesia to classify those cases suspected of being affected with BPS/IC. The time elapsed between onset of symptoms and diagnosis at the time of bladder biopsy was also defined as BPS/IC duration. Bladder biopsies were taken including detrusor muscle, three deep cold biopsies of posterior, anterior and lateral bladder wall. Results: Statistical analysis showed significant correlation between BPS/IC duration and the presence of Hunner’s lesions ( P<0.023). Hunner’s lesion with cystoscopy and histological evidence of urothelial denudation with bladder biopsy appear to be related to BPS/IC duration. Thus an early diagnosis allows an appropriate therapeutic approach to be started to prevent a more severe evolution of this multifaceted painful syndrome. Conclusions: Our study shows a correlation between the time of symptom onset and evidence of urothelial denudation and with detrusor mast cell count in the whole group of patients. BPS/IC duration did not seem to correlate with the severity of symptoms, but rather with the presence of associated diseases. Level of evidence: Not applicable for this multicentre audit.

scholarly journals Effect of Glycosaminoglycan Replacement on Markers of Interstitial Cystitis In Vitro

2020 ◽  
Vol 11 ◽  
Author(s):  
Peadar Rooney ◽  
Christina Ryan ◽  
Barry J. McDermott ◽  
Kapil Dev ◽  
Abhay Pandit ◽  
...  
Keyword(s):  
Cell Viability ◽  
Interstitial Cystitis ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Receptor Expression ◽  
Cell Growth And Migration ◽  
Bladder Pain ◽  
Inflammatory Models ◽  
And Migration

Aims: To examine the effect of three commercial intravesical formulations of glycosaminoglycan on in vitro inflammatory models of IC/BPS to better understand there effect on specific markers of disease.Methods: Human urothelial cells (HTB-4) were cultured under four conditions in the presence or absence of commercial GAG formulations. Cells were cultured under a basal condition or pre-treated with protamine sulfate (100 ng/ml) (damages the endogenous glycosaminoglycan layer), hydrogen peroxide (1%) (a metabolic stressor) or TNFα (10 ng/ml) (creating an inflammatory environment). Each of these four culture conditions was then treated with one of three GAG formulations, CystistatⓇ, iAluRilⓇ and HyacystⓇ. Assays were then performed to examine the effect of the exogenous GAGs on cell viability, cell migration, sGAG production, cytokine and gene expression.Results: All GAG formulations were well tolerated by the HTB-4 cells and supported cell growth and migration. iAluRilⓇ was most effective at stimulating endogenous sGAG production under all conditions, increasing sGAGs by up to 15-fold. All GAG formulations significantly reduced the production of the pro-inflammatory cytokine IL-8 under basal conditions, while no GAG treatment suppressed cytokine production under any other condition. Only CystistatⓇ had a significant effect on HA receptor expression, significantly increasing ICAM-1 expression at 3 h that returned to basal levels at 24 h. No GAG treatment significantly changed the expression of GAG synthesis enzymes (CSGALNACT1, CSGALNACT2) or markers of tissue remodeling (MMP2, TIMP1) and pain (COX-1/PTGS-1, NGF).Conclusions: The data presented in this study reveal that commercial intravesical formulation support cell viability and migration. In addition, the commercial GAG formulations have a mild anti-inflammatory effect in the in vitro model of interstitial cystitis/bladder pain syndrome.

scholarly journals New Aspects in the Differential Diagnosis and Therapy of Bladder Pain Syndrome/Interstitial Cystitis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Jochen Neuhaus ◽  
Thilo Schwalenberg ◽  
Lars-Christian Horn ◽  
Henry Alexander ◽  
Jens-Uwe Stolzenburg
Keyword(s):  
Differential Diagnosis ◽  
Interstitial Cystitis ◽  
Clinical Symptoms ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Clinical Diagnostics ◽  
Receptor Expression ◽  
Case Scenario ◽  
Worst Case ◽  
Bladder Pain

Diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is presently based on mainly clinical symptoms. BPS/IC can be considered as a worst-case scenario of bladder overactivity of unknown origin, including bladder pain. Usually, patients are partially or completely resistant to anticholinergic therapy, and therapeutical options are especially restricted in case of BPS/IC. Therefore, early detection of patients prone to develop BPS/IC symptoms is essential for successful therapy. We propose extended diagnostics including molecular markers. Differential diagnosis should be based on three diagnostical “columns”: (i) clinical diagnostics, (ii) histopathology, and (iii) molecular diagnostics. Analysis of molecular alterations of receptor expression in detrusor smooth muscle cells and urothelial integrity is necessary to develop patient-tailored therapeutical concepts. Although more research is needed to elucidate the pathomechanisms involved, extended BPS/IC diagnostics could already be integrated into routine patient care, allowing evidence-based pharmacotherapy of patients with idiopathic bladder overactivity and BPS/IC.

Mapping of Pain Phenotypes in Female Patients with Bladder Pain Syndrome/Interstitial Cystitis and Controls

2012 ◽  
Vol 62 (6) ◽  
pp. 1188-1194 ◽  
Author(s):  
Dean A. Tripp ◽  
J. Curtis Nickel ◽  
Jennifer Wong ◽  
Michel Pontari ◽  
Robert Moldwin ◽  
...  
Keyword(s):  
Interstitial Cystitis ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Female Patients

scholarly journals A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Chin-Li Chen ◽  
Chien-Chang Kao ◽  
Ming-Hsin Yang ◽  
Gang-Yi Fan ◽  
Juin-Hong Cherng ◽  
...  
Keyword(s):  
Growth Factors ◽  
Interstitial Cystitis ◽  
Bladder Wall ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Bladder Pain ◽  
Dextrose Solution ◽  
Cytokine Analysis ◽  
Limited Effectiveness ◽  
Significant Difference

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment’s efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.

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