Interstitial cystitis: bladder pain and beyond.

Tufts University School of Medicine, Department of Pharmacology and Experimental Therapeutics, Experimental Therapeutics 136 Harrison Avenue, Boston, MA 02111, USA.
Expert Opinion on Pharmacotherapy (Impact Factor: 3.09). 01/2009; 9(17):2979-94. DOI: 10.1517/14656560802519845
Source: PubMed

ABSTRACT Interstitial cystitis is characterized by over 6 months of chronic pain, pressure and discomfort felt in the lower pelvis or bladder. It is often relieved with voiding, along with daytime frequency and nocturia in the absence of a urinary tract infection. Interstitial cystitis occurs primarily in females including adolescents and its diagnosis is still one of exclusion. It is now recognized as a serious medical condition associated with significant disability.
The aim of this paper was to review the pathogenesis and treatment of interstitial cystitis with emphasis on new pathogenetic trends and therapeutic modalities.
About 713 mostly original papers were reviewed in Medline from 1990 to August. 2008. All authors independently reviewed the literature. Large, double-blind, placebo-controlled, clinical trials were few and the medical histories of the patients used varied considerably making conclusions difficult. Promising pilot trials turned out mostly negative on follow-up.
Increasing evidence of co-morbid diseases, neurogenic inflammation and the effect of stress are promising as new targets for pathophysiology. No new effective treatments have emerged. Oral pentosanpolysulfate, amitriptyline, hydroxyzine and quercetin, as well as intravesical heparin/bicarbonate/lidocaine solutions, are still used with variable success. Some pilot open-label trials presented encouraging findings.
Interstitial cystitis contributes substantially to chronic pelvic pain and to poor quality of life. Oral or intravesical administration of solutions containing sodium hyaluronate, chondroitin sulfate and quercetin to both reduce bladder inflammation and 'replenish' the glycosaminoglycan layer should be tried. There is a clear need for therapeutic modalities. New potential translational research areas are suggested.

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    ABSTRACT: We investigated the effect of the multi-herbal medicine, WSY-1075 in an animal model of hydrochloric acid (HCl)-induced cystitis. Rats were randomly assigned to three groups: sham-operated (control), HCl-induced only (HC), and HC treated with WSY-1075 (HC + WT). Oral administration of either distilled water (control, HC) or WSY-1075 (400 mg/kg) was continued for 4 weeks. In HC and HC + WT groups, cystitis was induced with 0.4 M HCl beginning on the 22nd day. Rats in each group underwent cystometrography, and bladders were examined for evidence of inflammation and oxidative stress. Treatment with WSY-1075 decreased the frequency of urination and reduced inflammation of the bladder tissue in a rat model of HCl-induced cystitis. Compared with the control group, the HC group showed severe chronic inflammatory and fibrosis signs, and the inflammatory grades significantly decreased following WSY-1075 treatment in the HC-WT group. The HC + WT group showed a markedly decreased expression of pro-inflammatory cytokines compared to the HC group. The level of malondialdehyde was significantly greater in the HC group compared to the control group, and it was significantly reduced in the treated (HC + WT) group. The levels of superoxide dismutase increased in the HC + WT group, which confirmed the anti-oxidant effect of WSY-1075. We suggest that reduction of oxidative stress may play a role in this anti-inflammatory effect. Neurourol. Urodynam. © 2013 Wiley Periodicals, Inc.
    Neurourology and Urodynamics 10/2013; DOI:10.1002/nau.22507 · 2.46 Impact Factor
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    ABSTRACT: Objectives To compare the different endovesical therapeutic regimes in terms of clinical effectiveness based on glycosaminoglycan replenishment agents (RA-GAG) available on the market in Spain.Material and methodsA bibliographic analysis was made of the studies published in Medline from 1996 to 2012 on RA-GAG of application in the bladder, placing emphasis on the clinical results. A post-hoc comparison was made of the efficacy of this treatment in the studies conducted in patients with interstitial cystitis in different conditions by calculating the effect sizes to analyze improvement on the pain visual analogue scale (VAS) and clinical response rate. The number of patients needed to treat (NNT) for the different agents was calculated based on the odds ratio and associated economic implications.ResultsThe globally available evidence is scarce. There are 38 articles about RA-GAGs in different indications, 71 of them in interstitial cystitis and only 8 may assist in establishing a comparison between the results presented. The treatments used were placebo, 0.8% high molecular weight hyaluronic acid (Cystistat®), 2% chondroitin sulfate sodium (Uracyst®) and a combination of 1.6% low molecular weight hyaluronic acid plus 2% chondroitin sulfate (Ialuril®), between 6 and 12 instillations. Another low molecular weight hyaluronic acid preparation (Uromac®) lacks any scientific evidence. All the therapeutic elements studied show a mean score decrease on the pain VAS and increase in the rate of post-treatment response. The NNT for the treatments that are statistically more beneficial over placebo ranges from 1.6 and 4.1. The post-hoc comparison of the response rates has established that Cystistat® 12 instillations (OR 18.8; 95% CI 6.4-57.2; P = .001) or 10 instillations (OR 19.2; 95% CI 5.3-75.3; P = .001) are the treatment regimes that obtain maximum effectiveness. In both cases, the NNT was 1.6.Conclusions This study has multiple limitations inherent to the nature of the design. However, although the available literature is scarce, it shows that there are differences regarding the clinical effectiveness of the different agents and regimes used for endovesical treatment of interstitial cystitis. These differences also entail economic type implications.
    Actas urologicas españolas 02/2013; 37(2):92–99. DOI:10.1016/j.acuro.2012.10.002 · 1.15 Impact Factor
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    ABSTRACT: Interstitial cystitis is a debilitating bladder inflammation disorder. To date, the understanding of the causes of interstitial cystitis remains largely fragmentary and there is no effective treatment available. Recent experimental results have shown a functional role of the endocannabinoid system in urinary bladder. In this study, we evaluated the anti-inflammatory effect of selective cannabinoid CB1 and CB2 receptor agonists in a mouse model of interstitial cystitis. Bladder inflammation was induced in mice by lipopolysaccharide (LPS) and whole bladders were removed 24h later. LPS induced a significant increase of the contractile amplitude in spontaneous activity and a hypersensitivity to exogenous acetylcholine-induced contraction of whole-isolated bladder. Next, we evaluated the anti-inflammatory activity of cannabinoidergic compounds by pretreating mice with CB1 or CB2 selective agonist compounds, respectively ACEA and JWH015. Interestingly, JWH015, but not ACEA, antagonized LPS-induced bladder inflammation. Additionally, anti-inflammatory activity was studied by evaluation, leukocytes mucosa infiltration, myeloperoxidase activity, and mRNA expression of pro-inflammatory interleukin (IL-1α and IL-1β), tumor necrosis factor-alpha (TNF-α) and cannabinoid CB1 and CB2 receptors. JWH015 significantly decreased leukocytes infiltration in both submucosa and mucosa, as well as the myeloperoxydase activity, in LPS treated mice. JWH015 reduced mRNA expression of IL-1α, IL-1β, and TNF-α. LPS treatment increased expression of bladder CB2 but not CB1 mRNA. Taken together, these findings strongly suggest that modulation of the cannabinoid CB2 receptors might be a promising therapeutic strategy for the treatment of bladder diseases and conditions characterized by inflammation, such as interstitial cystitis.
    European journal of pharmacology 02/2014; 729. DOI:10.1016/j.ejphar.2014.02.013 · 2.68 Impact Factor

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