Bladder pain syndrome/interstitial cystitis as a functional somatic syndrome

The pathophysiological mechanisms underlying overactive bladder syndrome (OAB) can include dysfunction of sensory pathways of the peripheral and central nervous systems, resulting in bladder hypersensitivity. Central sensitization describes an induced state of spinal hypersensitivity that is associated with a variety of chronic pain disorders that share many attributes with OAB, albeit without the presence of pain. As such, the concept of central sensitization might be relevant to understanding the mechanisms and clinical manifestations of OAB syndrome. An understanding of the pathophysiology and clinical manifestations of central sensitization, and the evidence that supports a role of central sensitization in OAB, including the potential implications of mechanisms of central sensitization for the treatment of patients with OAB could provide a novel approach to the treatment of patients with this disease. Such an approach would be especially relevant to those patients with central sensitization-related comorbidities, and has the potential to improve the outcomes of these patients in particular.

BackgroundInterstitial cystitis (IC) is a chronic inflammation disorder mainly within the submucosal and muscular layers of the bladder. As the cause of IC remains unknown, no effective treatments are currently available. Administration of stem cell provides a potential for treatment of IC.MethodsThis study was conducted using urine-derived stem cells (USCs) for protamine/lipopolysaccharide (PS/LPS)-induced interstitial cystitis in a rodent model. In total, 60 female Sprague–Dawley rats were randomized into three experimental groups (n = 5/group): sham controls; IC model alone; and IC animals intravenously treated with USCs (1.2 × 106 suspended in 0.2 ml phosphate-buffered saline (PBS).ResultsOur data showed that the bladder micturition function was significantly improved in IC animals intravenously treated with USCs compared to those in the IC model alone group. The amount of antioxidants and antiapoptotic protein biomarkers heme oxygenase (HO)-1, NAD(P)H quinine oxidoreductase (NQO)-1, and Bcl-2 within the bladder tissues were significantly higher in IC animals intravenously treated with USCs and lower in the sham controls group as assessed by Western blot and immunofluorescent staining. In addition, the expression of autophagy-related protein LC3A was significantly higher in the IC model alone group than that in IC animals intravenously treated with USCs. Inflammatory biomarkers and apoptotic biomarkers (interleukin (IL)-6, tumor necrosis factor (TNF)α, nuclear factor (NF)-κB, caspase 3, and Bax) and the downstream inflammatory and oxidative stress biomarkers (endoplasmic reticulum stress and autophagy-related protein (GRP78, LC3, Beclin1)) in the bladder tissue revealed statistically different results between groups.ConclusionsUSCs restored the bladder function and histological construction via suppressing oxidative stress, inflammatory reaction, and apoptotic processes in a PS/LPS-induced IC rodent model, which provides potential for treatment of patients with IC.

Context: Interstitial cystitis is a multifactorial chronic and debilitating disease which is commonly associated with pain localized in the bladder region, increased urinary frequency, urgency and nocturia. Due to the high prevalence of pain in the population affected more recently the condition is often referred to as interstitial cystitis / bladder pain syndrome (IC/BPS). Evidence Acquisition: Although IC presents with many different symptoms, researchers have formulated three different theories, which are not mutually exclusive, to explain IC pathology: the first is related to the alteration of the proteoglycan and protein junction composition, structure and presence in the urothelium. The second is an immune induced IC resulting from an increased number of activated mast cells in the bladder internal layers, such as detrusor muscle (DM), and mucosa/submucosa. The third type, which is closely related to the second one, is due to a sensory nerve sensitization as an effect of neurotrophic factors molecule release. Results: Previous classification has been mirrored in the development of various in vitro and in vivo disease models created to mimic IC, as well as in the available therapies used to treat the condition to date. Conclusions: This review will summarize the most recent advances in the field, related to the different causative factors contributing to the development of the condition, the in vivo models used as well as the evidence they provide in advancing our knowledge and their limitations. The focus will be on works reporting on IC in the domain related to alterations in proteoglycans and cellular junction, specifically their composition, structure and appearance in the urothelium, and also discuss present and future therapies. Conclusions: This review will summarize the most recent advances in the field, related to the different causative factors contributing to the development of the condition, the in vivo models used as well as the evidence they provide in advancing our knowledge and their limitations. The focus will be on works reporting on IC in the domain related to alterations in proteoglycans and cellular junction, specifically their composition, structure and appearance in the urothelium, and also discuss present and future therapies.