Materiały źródłowe

• #1 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #2 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. […] Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. […] This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. […] Several possible pathogeneses of IC/BPS have been proposed based on patients’ medical history, histopathological bladder findings, urinary biomarker analysis, and immunohistochemical studies. Various conditions may contribute to the development of IC/BPS, including autoimmune reactions after acute bacterial cystitis; mast cell activation due to toxins, stress, or allergies; urothelial dysfunction after bladder wall injury; neurogenic activation through the upregulated release of sensory fibers by neuropeptides; and central sensitization.

• #3 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium.

• #4 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Increased urothelial permeability due to diminished GAG levels and ultrastructural abnormalities are seen on biopsies with a loss of tight junctions and adhesive junction proteins. This causes a loss of mucosal barrier protection, resulting in a „leaky urothelium.” […] Fibrosis also results from the chronic inflammatory process, evident by the upregulation of extracellular matrix proteins, increased myofibroblasts, and decreased capillary density, which reduce bladder capacity and lead to further stretching and stimulation of afferent sensory pain fibers. […] The underlying pathophysiology of IC/BPS is somewhat uncertain, contributing to the lack of a definitive, curative remedy. Known involved bladder pathological findings include chronic inflammation, afferent sensory hyperactivity, nociceptor upregulation, mast cell overactivity, submucosal microvascular abnormalities, autoimmune disorders, lack of normal bladder epithelial cell growth, and urothelial thinning with a deficient or dysfunctional superficial mucosal GAGs layer.

• #5 Interstitial Cystitis and Chronic Pain Syndrome

  https://www.uspharmacist.com/article/interstitial-cystitis-and-chronic-pain-syndrome

  IC/PBS is a chronic disease of unknown etiology; however, several theories exist, and the pathophysiology of IC/PBS is considered to be multifactorial. […] Although the underlying pathophysiology of IC/PBS is not completely understood, it is thought to involve changes in the bladder urothelium, mast-cell activation, and neurogenic inflammation. The normal bladder urothelium is highly impermeable to urinary solutes and irritants such as urea, ammonia, and potassium. The glycosaminoglycan (GAG) layer is responsible for protecting the bladder surface from irritants. Deficiency of the GAG layer results in increased urothelial permeability, which allows irritants to leak from the urine into the bladder tissue. This results in symptoms of IC/PBS, such as pelvic pain and irritative voiding symptoms. In addition to the changes in the bladder urothelium, mast-cell activation is increased, which can lead to more mast-cell upregulation, inflammation of the bladder wall, injury to the GAG layer, and eventually fibrotic changes within the bladder wall.

• #6 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  Interstitial cystitis (IC) is a heterogeneous syndrome characterized by bladder pain and is associated with frequency and nocturia. Research findings have proposed several pathophysiological mechanisms including epithelial dysfunction, activation of mast cells, neurogenic inflammation, autoimmunity, and occult infection. […] One of the most common findings in IC bladders is denudation or thinning of the bladder epithelium, suggesting an altered regulation of urothelial homeostasis. […] Augmented purinergic signaling in the bladder has been found in IC. […] Abnormal cytokine secretion in IC bladders has also been related to an increase in purinergic signaling, which mediates increased bladder sensation. […] The increased apoptosis of urothelium has been associated with increased tryptase activity and clinical bladder pain scores, suggesting chronic inflammation, increased apoptosis, and abnormal urothelial function are closely associated in IC bladders.

• #7 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Increased urothelial permeability due to diminished GAG levels and ultrastructural abnormalities are seen on biopsies with a loss of tight junctions and adhesive junction proteins. This causes a loss of mucosal barrier protection, resulting in a „leaky urothelium.” […] Fibrosis also results from the chronic inflammatory process, evident by the upregulation of extracellular matrix proteins, increased myofibroblasts, and decreased capillary density, which reduce bladder capacity and lead to further stretching and stimulation of afferent sensory pain fibers. […] The underlying pathophysiology of IC/BPS is somewhat uncertain, contributing to the lack of a definitive, curative remedy. Known involved bladder pathological findings include chronic inflammation, afferent sensory hyperactivity, nociceptor upregulation, mast cell overactivity, submucosal microvascular abnormalities, autoimmune disorders, lack of normal bladder epithelial cell growth, and urothelial thinning with a deficient or dysfunctional superficial mucosal GAGs layer.

• #8 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Increased urothelial permeability due to diminished GAG levels and ultrastructural abnormalities are seen on biopsies with a loss of tight junctions and adhesive junction proteins. This causes a loss of mucosal barrier protection, resulting in a „leaky urothelium.” […] Fibrosis also results from the chronic inflammatory process, evident by the upregulation of extracellular matrix proteins, increased myofibroblasts, and decreased capillary density, which reduce bladder capacity and lead to further stretching and stimulation of afferent sensory pain fibers. […] The underlying pathophysiology of IC/BPS is somewhat uncertain, contributing to the lack of a definitive, curative remedy. Known involved bladder pathological findings include chronic inflammation, afferent sensory hyperactivity, nociceptor upregulation, mast cell overactivity, submucosal microvascular abnormalities, autoimmune disorders, lack of normal bladder epithelial cell growth, and urothelial thinning with a deficient or dysfunctional superficial mucosal GAGs layer.

• #9 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] The inflammatory reaction may extend into the dorsal horn ganglia and the corresponding sacral cord, resulting in central sensitization and multiple functional somatic symptoms, such as pelvic floor, urethral, or pelvic pain. […] The urothelium in IC/BPS bladders is impaired in isolating urine and the bladder wall, which prevents the influx of urinary acid, potassium, and toxins into the suburothelial space. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Increased expression of the inflammatory marker tryptase in the suburothelium has been associated with the increased expression of the apoptotic marker terminal deoxynucleotidyl transferase, decreased expression of the proliferation marker Ki-67, and decreased expression of the adhesive proteins E-cadherin and zonula occludens-1.

• #10 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization.

• #11 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium.

• #12 Review of intravesical therapies for bladder pain syndrome/interstitial cystitis – Cvach – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8189/html

  Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain syndrome characterised by pain/discomfort attributed to the bladder, with associated urgency and urinary frequency. […] The underlying etiology of BPS/IC is not well understood and it is likely that a number of mechanisms play a role in the development of the condition. The urothelium/transitional epithelium is thought to play a fundamental role in the pathogenesis of BPS/IC. […] Once the subepithelial cells come into contact with urinary solutes, an inflammatory reaction is triggered, in turn resulting in decreased urothelial production of GAG and exacerbation of urothelial permeability and inflammation. Urothelial damage results in pathologic C-fiber activation, causing smooth muscle contraction, neurogenic inflammation, and hypersensitivity.

• #13 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Interstitial cystitis (IC) is a bladder syndrome of unknown etiology. The pathogenesis and etiology of interstitial cystitis remain incompletely defined. However, there is an emerging consensus as to the central role of epithelial dysfunction, bladder sensory nerve up-regulation, and mast cell activation in the genesis of IC. […] Changes in this surface can cause permeability alterations that allow potassium ions to traverse the urothelium, depolarize sensory and motor nerves, and activate mast cells. This permeability dysfunction is manifested by increased urea absorption and positive potassium sensitivity tests in IC patients. […] Urinary antiproliferative factor (APF), recently described in IC, inhibits cell proliferation and impairs repair of damaged or denuded urothelium with resulting changes in the barrier function of the urothelium.

• #14 Internet Scientific Publications

  https://ispub.com/IJU/7/1/3195

  Other studies have shown the presence of antiproliferative factor (APF), in the urine of IC patients that inhibits the proliferation of normal human bladder epithelial cells in vitro. […] The theory that IC urine contains toxic factors is also supported by the fact that bladder tissues treated with urine from IC patients showed increased expression of a stress protein (heat shock protein, 72 kDa HSP). […] A defect in this protective layer could permit pathogens leak into the subepithelial space and the muscularis, possibly injuring muscle and/or initiating sensory stimulation causing symptoms of IC. […] It has been proposed that IC may develop as a consequence of urothelial injury that persists after infectious agents are no longer present. […] Certain inflammatory mediators, such as substance P and bradykinin also function as nociceptive neurotransmitters.

• #15 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] The inflammatory reaction may extend into the dorsal horn ganglia and the corresponding sacral cord, resulting in central sensitization and multiple functional somatic symptoms, such as pelvic floor, urethral, or pelvic pain. […] The urothelium in IC/BPS bladders is impaired in isolating urine and the bladder wall, which prevents the influx of urinary acid, potassium, and toxins into the suburothelial space. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Increased expression of the inflammatory marker tryptase in the suburothelium has been associated with the increased expression of the apoptotic marker terminal deoxynucleotidyl transferase, decreased expression of the proliferation marker Ki-67, and decreased expression of the adhesive proteins E-cadherin and zonula occludens-1.

• #16 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. […] The known pathological findings from the bladders of IC/BPS patients included urothelial denudation, chronic inflammation, and sensory afferent activation. […] The prominent pathological findings of IC/BPS bladders include chronic inflammation and urothelial denudation. Inflammation is higher in bladders with Hunner’s lesions (HIC) compared with inflammation in non-Hunner’s IC (NHIC). […] The severity of bladder wall inflammation is highly associated with the severity of IC symptoms, glomerulation grade, and maximal bladder capacity under cystoscopic hydrodistention in bladder-centered IC/BPS patients, which indicates the pathological lesions are located inside the urinary bladder.

• #17

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  Aberrant urothelial HLA-DR expression was found in all but one of the IC cases in which the urothelium was not denuded. […] Furthermore, the urothelium and submucosa in IC was infiltrated by CD4+, CD8+ and T cells, plasma cells, mast cells and macrophages. […] The precise aetiology of IC remains obscure although this study has revealed a genetic predisposition to the development of IC and has demonstrated immunological autoreactive mechanisms in the pathogenesis of this condition.

• #18 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  The cause of interstitial cystitis is unknown. […] Several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. […] Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. […] Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC. […] Most literature supports the belief that IC’s symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladdera breakdown of the bladder lining (also known as the adherence theory).

• #19 Interstitial Cystitis: Urgency and Frequency Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1001/p1199.html

  Another working theory of interstitial cystitis etiology includes mast cell abnormalities. […] Increased numbers of submucosal mast cells are found in these patients. […] Antigenic exposure of mast cells causes the release of pharmacologically active mediators (e.g., histamine, prostaglandins, leukotrienes and tryptases) that have a significant effect on smooth muscle, vascular epithelium and inflammation.

• #20 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] The inflammatory reaction may extend into the dorsal horn ganglia and the corresponding sacral cord, resulting in central sensitization and multiple functional somatic symptoms, such as pelvic floor, urethral, or pelvic pain. […] The urothelium in IC/BPS bladders is impaired in isolating urine and the bladder wall, which prevents the influx of urinary acid, potassium, and toxins into the suburothelial space. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Increased expression of the inflammatory marker tryptase in the suburothelium has been associated with the increased expression of the apoptotic marker terminal deoxynucleotidyl transferase, decreased expression of the proliferation marker Ki-67, and decreased expression of the adhesive proteins E-cadherin and zonula occludens-1.

• #21 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Other findings associated with chronic bladder inflammation include decreased mucosal protection from GAGs loss or dysfunction, lower adhesive protein E-cadherin, decreased basal cell growth, defective umbrella cell integrity, abnormal apical cell maturation, and increased urothelial cell apoptosis. […] The increased serum levels of C-reactive protein and pro-inflammatory cytokines also point to inflammation as a primary underlying etiology of IC/BPS. […] IC/BPS can appear as two separate entities: the IC entity clearly demonstrates an inflammatory component that is mostly missing in those with the predominantly BPS entity. […] Chronic stress is found in 50% of IC/BPS patients, which is a factor in the development and exacerbation of symptoms. […] The chronic pain typically associated with IC/BPS is caused by sensory afferent nerve activity and central nervous system sensitization.

• #22 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #23 Interstitial Cystitis: Urgency and Frequency Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2001/1001/p1199.html

  Another working theory of interstitial cystitis etiology includes mast cell abnormalities. […] Increased numbers of submucosal mast cells are found in these patients. […] Antigenic exposure of mast cells causes the release of pharmacologically active mediators (e.g., histamine, prostaglandins, leukotrienes and tryptases) that have a significant effect on smooth muscle, vascular epithelium and inflammation.

• #24 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues. […] Numerous studies have noted the link between IC, anxiety, stress, hyper-responsiveness, panic, and abuse. […] Another proposed mechanism for interstitial cystitis is the autoimmune mechanism. […] Biopsies on the bladder walls of people with IC may contain mast cells. […] The activation of mast cells triggers the release of histamine, amongst other inflammatory mediators. […] Additionally, another proposed mechanism is increased activity of unspecified nerves in the bladder wall. […] An unknown toxin or stimuli may activate nerves within the bladder wall, causing the release of neuropeptides. These neuropeptides can induce a secondary cascade which stimulates pain in the bladder wall.

• #25 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. […] Hunner’s (HIC) and non-Hunner’s IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. […] This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. […] Several possible pathogeneses of IC/BPS have been proposed based on patients’ medical history, histopathological bladder findings, urinary biomarker analysis, and immunohistochemical studies. Various conditions may contribute to the development of IC/BPS, including autoimmune reactions after acute bacterial cystitis; mast cell activation due to toxins, stress, or allergies; urothelial dysfunction after bladder wall injury; neurogenic activation through the upregulated release of sensory fibers by neuropeptides; and central sensitization.

• #26

  https://www.ics.org/2022/abstract/27

  Hypothesis / aims of study Interstitial cystitis/Bladder pain syndrome (IC/ BPS) is a chronic debilitating inflammatory disease of the urinary bladder that significantly affects the quality of life. […] The pathophysiology of IC/BPS is elusive and rather multifactorial, in which a defect in the bladder urothelium and chronic inflammation of bladder wall are key features. […] The urothelial barrier defect is associated with increased urothelial permeability, allowing harmful urinary constituents to penetrate the bladder wall and depolarise the nociceptive sensory nerve fibres, which release neuroactive substances including SP, inducing mast cell degranulation and tissue inflammation. […] MRGPRX2 is a recently identified G-protein coupled receptor involved in mast cell responsiveness to SP in different chronic inflammatory conditions, and its expression is associated with increased tissue inflammation.

• #27 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. […] The known pathological findings from the bladders of IC/BPS patients included urothelial denudation, chronic inflammation, and sensory afferent activation. […] The prominent pathological findings of IC/BPS bladders include chronic inflammation and urothelial denudation. Inflammation is higher in bladders with Hunner’s lesions (HIC) compared with inflammation in non-Hunner’s IC (NHIC). […] The severity of bladder wall inflammation is highly associated with the severity of IC symptoms, glomerulation grade, and maximal bladder capacity under cystoscopic hydrodistention in bladder-centered IC/BPS patients, which indicates the pathological lesions are located inside the urinary bladder.

• #28 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  Increased microvascular endothelial cell apoptosis in IC bladders causes glomerulations, and impaired urothelial homeostasis is associated with chronic bladder inflammation. […] Chronic pain in patients with IC/BPS is likely caused by central nervous system (CNS) sensitization and activation of sensory afferent nerves. […] Bladder epithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult infection may also cause bladder pain. […] The treatment of IC/BPS should follow the possible pathophysiology and specific clinical presentation. Because the actual etiology and diagnosis of IC/BPS remain unclear, treatments usually target the pathogenesis, including the post-infection autoimmune process, mast cell activation, urothelial dysfunction, and neurogenic inflammation.

• #29 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Up-regulation of histaminergic and muscarinic neurotransmitter receptors has been demonstrated in IC/BPS and may contribute to the pain, urgency, and frequency. Additionally, up-regulation of neural afferent pathways has been shown in IC/BPS, as well as a central hyperresponsiveness in association with other conditions, including fibromyalgia, irritable bowel syndrome, and depression/anxiety disorders. […] Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder overdistention. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types. Such differences may have important implications for diagnosis and therapy. Evidence showing progression of ulcerative to nonulcerative disease, or vice versa, is lacking.

• #30 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #31 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  Increased microvascular endothelial cell apoptosis in IC bladders causes glomerulations, and impaired urothelial homeostasis is associated with chronic bladder inflammation. […] Chronic pain in patients with IC/BPS is likely caused by central nervous system (CNS) sensitization and activation of sensory afferent nerves. […] Bladder epithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult infection may also cause bladder pain. […] The treatment of IC/BPS should follow the possible pathophysiology and specific clinical presentation. Because the actual etiology and diagnosis of IC/BPS remain unclear, treatments usually target the pathogenesis, including the post-infection autoimmune process, mast cell activation, urothelial dysfunction, and neurogenic inflammation.

• #32 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  The cause of interstitial cystitis is unknown. […] Several explanations have been proposed and include the following: autoimmune theory, nerve theory, mast cell theory, leaky lining theory, infection theory, and a theory of production of a toxic substance in the urine. […] Evidence from clinical and laboratory studies confirms that mast cells play a central role in IC/BPS possibly due to their ability to release histamine and cause pain, swelling, scarring, and interfere with healing. […] Research has shown a proliferation of nerve fibers is present in the bladders of people with IC which is absent in the bladders of people who have not been diagnosed with IC. […] Most literature supports the belief that IC’s symptoms are associated with a defect in the bladder epithelium lining, allowing irritating substances in the urine to penetrate into the bladdera breakdown of the bladder lining (also known as the adherence theory).

• #33 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Up-regulation of histaminergic and muscarinic neurotransmitter receptors has been demonstrated in IC/BPS and may contribute to the pain, urgency, and frequency. Additionally, up-regulation of neural afferent pathways has been shown in IC/BPS, as well as a central hyperresponsiveness in association with other conditions, including fibromyalgia, irritable bowel syndrome, and depression/anxiety disorders. […] Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder overdistention. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types. Such differences may have important implications for diagnosis and therapy. Evidence showing progression of ulcerative to nonulcerative disease, or vice versa, is lacking.

• #34 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #35

  https://www.ics.org/2022/abstract/27

  Hypothesis / aims of study Interstitial cystitis/Bladder pain syndrome (IC/ BPS) is a chronic debilitating inflammatory disease of the urinary bladder that significantly affects the quality of life. […] The pathophysiology of IC/BPS is elusive and rather multifactorial, in which a defect in the bladder urothelium and chronic inflammation of bladder wall are key features. […] The urothelial barrier defect is associated with increased urothelial permeability, allowing harmful urinary constituents to penetrate the bladder wall and depolarise the nociceptive sensory nerve fibres, which release neuroactive substances including SP, inducing mast cell degranulation and tissue inflammation. […] MRGPRX2 is a recently identified G-protein coupled receptor involved in mast cell responsiveness to SP in different chronic inflammatory conditions, and its expression is associated with increased tissue inflammation.

• #36 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  The initial bladder insult may trigger an inflammatory cascade that causes local and central inflammation and the subsequent manifestation of clinical symptoms. […] The inflammatory reaction may extend into the dorsal horn ganglia and the corresponding sacral cord, resulting in central sensitization and multiple functional somatic symptoms, such as pelvic floor, urethral, or pelvic pain. […] The urothelium in IC/BPS bladders is impaired in isolating urine and the bladder wall, which prevents the influx of urinary acid, potassium, and toxins into the suburothelial space. […] Chronic inflammation of the bladder wall is the fundamental pathophysiology of IC/BPS. […] Increased expression of the inflammatory marker tryptase in the suburothelium has been associated with the increased expression of the apoptotic marker terminal deoxynucleotidyl transferase, decreased expression of the proliferation marker Ki-67, and decreased expression of the adhesive proteins E-cadherin and zonula occludens-1.

• #37 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #38 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #39 Internet Scientific Publications

  https://ispub.com/IJU/7/1/3195

  Increased numbers of mast cells have been demonstrated within the detrusor layer of the bladder in IC patients. […] Many of the clinical features of IC suggest that autoimmunity may play a role in the chronic inflammatory component of the disease. […] The development of new and more effective treatments modalities for IC has been severely hampered by the lack of experimental models. […] The etiology of IC remains elusive.

• #40

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  Aberrant urothelial HLA-DR expression was found in all but one of the IC cases in which the urothelium was not denuded. […] Furthermore, the urothelium and submucosa in IC was infiltrated by CD4+, CD8+ and T cells, plasma cells, mast cells and macrophages. […] The precise aetiology of IC remains obscure although this study has revealed a genetic predisposition to the development of IC and has demonstrated immunological autoreactive mechanisms in the pathogenesis of this condition.

• #41 Pathology of Cystitis: Overview, Etiology, Gross Findings

  https://emedicine.medscape.com/article/2055346-overview

  Cystitis describes a broad range of diseases with diverse etiology and pathologic mechanisms but with similar clinical presentations. […] The etiology of interstitial cystitis is not fully understood. Epidemiologic studies, however, have shown that affected individuals are more likely to have a history of childhood bladder problems or urinary tract infections. […] Other etiologies have also been suggested, such as an unidentified infectious agent or a defective epithelial cell layer, with the latter allowing toxic substances to enter the bladder wall and trigger the symptoms. Furthermore, the role of mast cells and abnormalities in the central nervous system (CNS) has been proposed in the pathogenesis of interstitial cystitis as well. […] Gene expression profiles from bladder biopsies in patients with ulcerative interstitial cystitis have shown a similar expression pattern to those of patients with immune system, lymphatic, and autoimmune diseases. The majority of the upregulated genes were expressed in the leukocytes, suggesting that leukocyte invasion of the bladder wall is important in the pathomechanism of ulcerative interstitial cystitis.

• #42 Bladder Pain Syndrome vs Interstitial Cystitis | Aare Urocare

  https://aareurology.sg/conditions/bladder-pain-syndrome-bps-vs-interstitial-cystitis-ic/

  The exact cause of BPS is uncertain. In most cases, the bladder is found to be normal whereas for IC, the bladder can be inflamed, ulcerated, scarred, or stiff. As such, researchers postulated several theories that may help to explain the damage to the bladder lining leading to the manifestation of the condition. […] Factors that may contribute to interstitial cystitis (IC): […] Inflammation can release chemicals that disrupt the integrity of the bladders epithelial surface leading to mast cell activation and ultimately giving rise to pain and voiding dysfunction. […] A defect in Tamm-Horsfall protein can lead to the development of interstitial cystitis. […] An autoimmune disorder may cause the immune system to attack the bladder mistakenly. CD8+, CD4+, and B lymphocytes, plasma cells, and immunoglobulins were found to bind to the epithelial surface of the bladder in patients with interstitial cystitis.

• #43 Bladder Pain Syndrome vs Interstitial Cystitis | Aare Urocare

  https://aareurology.sg/conditions/bladder-pain-syndrome-bps-vs-interstitial-cystitis-ic/

  The exact cause of BPS is uncertain. In most cases, the bladder is found to be normal whereas for IC, the bladder can be inflamed, ulcerated, scarred, or stiff. As such, researchers postulated several theories that may help to explain the damage to the bladder lining leading to the manifestation of the condition. […] Factors that may contribute to interstitial cystitis (IC): […] Inflammation can release chemicals that disrupt the integrity of the bladders epithelial surface leading to mast cell activation and ultimately giving rise to pain and voiding dysfunction. […] A defect in Tamm-Horsfall protein can lead to the development of interstitial cystitis. […] An autoimmune disorder may cause the immune system to attack the bladder mistakenly. CD8+, CD4+, and B lymphocytes, plasma cells, and immunoglobulins were found to bind to the epithelial surface of the bladder in patients with interstitial cystitis.

• #44 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #45 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #46

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) is still unclear. […] However, viral infection in the bladder might be a pathogenic factor for IC/BPS. […] The presence of urinary tract viruses in patients with IC/BPS has been sporadically investigated since the 1970s. […] With polymerase chain reaction, several studies have reported increased papillomavirus, BK virus, and John Cunningham virus viral load in urine samples from patients with IC/BPS. […] The presence of urinary papillomavirus was associated with more severe IC/BPS symptoms. […] Enriched viral infection-associated gene pathways in patients with IC/BPS were noted in the studies, including cytomegalovirus infection, Kaposi sarcoma-associated herpesvirus infection, human papillomavirus infection, and EpsteinBarr virus (EBV) infection.

• #47

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) is still unclear. […] However, viral infection in the bladder might be a pathogenic factor for IC/BPS. […] The presence of urinary tract viruses in patients with IC/BPS has been sporadically investigated since the 1970s. […] With polymerase chain reaction, several studies have reported increased papillomavirus, BK virus, and John Cunningham virus viral load in urine samples from patients with IC/BPS. […] The presence of urinary papillomavirus was associated with more severe IC/BPS symptoms. […] Enriched viral infection-associated gene pathways in patients with IC/BPS were noted in the studies, including cytomegalovirus infection, Kaposi sarcoma-associated herpesvirus infection, human papillomavirus infection, and EpsteinBarr virus (EBV) infection.

• #48

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) is still unclear. […] However, viral infection in the bladder might be a pathogenic factor for IC/BPS. […] The presence of urinary tract viruses in patients with IC/BPS has been sporadically investigated since the 1970s. […] With polymerase chain reaction, several studies have reported increased papillomavirus, BK virus, and John Cunningham virus viral load in urine samples from patients with IC/BPS. […] The presence of urinary papillomavirus was associated with more severe IC/BPS symptoms. […] Enriched viral infection-associated gene pathways in patients with IC/BPS were noted in the studies, including cytomegalovirus infection, Kaposi sarcoma-associated herpesvirus infection, human papillomavirus infection, and EpsteinBarr virus (EBV) infection.

• #49

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) is still unclear. […] However, viral infection in the bladder might be a pathogenic factor for IC/BPS. […] The presence of urinary tract viruses in patients with IC/BPS has been sporadically investigated since the 1970s. […] With polymerase chain reaction, several studies have reported increased papillomavirus, BK virus, and John Cunningham virus viral load in urine samples from patients with IC/BPS. […] The presence of urinary papillomavirus was associated with more severe IC/BPS symptoms. […] Enriched viral infection-associated gene pathways in patients with IC/BPS were noted in the studies, including cytomegalovirus infection, Kaposi sarcoma-associated herpesvirus infection, human papillomavirus infection, and EpsteinBarr virus (EBV) infection.

• #50

  https://link.springer.com/article/10.1007/s11884-023-00713-7

  Our recent studies reported the presence of EBV in IC/BPS bladders, especially in patients with IC/BPS with Hunners lesion (HIC). […] EBV latency and lytic infection were observed in HIC bladders, indicating EBV infection persistence and reactivation. […] EBV latency infection in B cells could induce brain-derived neurotrophic factor overexpression and might cause nerve hyperplasia in IC/BPS bladders. […] The presence of urinary virus in the patients with IC/BPS suggested that viral infection might be a pathogenic factor in patients with IC/BPS. […] Molecular evidence from IC/BPS bladder tissue also showed that viral infection may involve the pathogenesis of IC/BPS. […] Further studies are needed to clarify the mechanism.

• #51 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #52 Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/interstitial-cystitis-bladder-pain-syndrome-clinical-features-and-diagnosis

  Chronic bladder pain can be a debilitating condition that impacts quality of life. The pathophysiology of chronic bladder pain is not well understood, and symptoms likely represent more than one underlying etiology. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a diagnosis that applies to patients with chronic bladder pain in the absence of other explanatory etiologies. Identification of patients who meet diagnostic criteria for IC/BPS allows for treatment with the goal of providing symptomatic relief. This condition often coexists with other chronic pain syndromes (eg, fibromyalgia, irritable bowel syndrome). […] The pathogenesis, clinical features, and diagnosis of IC/BPS will be discussed here. Management of this condition is reviewed separately. Chronic bladder pain in the absence of an identifiable etiology has historically been called interstitial cystitis. This term is a misnomer, however, since there is no clear evidence that bladder inflammation (cystitis) is involved in the etiology or pathophysiology of the condition, nor is there evidence that the condition is reliably associated with abnormalities of the interstitium of the bladder.

• #53 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  Up-regulation of histaminergic and muscarinic neurotransmitter receptors has been demonstrated in IC/BPS and may contribute to the pain, urgency, and frequency. Additionally, up-regulation of neural afferent pathways has been shown in IC/BPS, as well as a central hyperresponsiveness in association with other conditions, including fibromyalgia, irritable bowel syndrome, and depression/anxiety disorders. […] Clinically, interstitial cystitis is often divided into 2 distinct subgroups based on findings at cystoscopy and bladder overdistention. These categories are the ulcerative (ie, classic) and nonulcerative (ie, Messing-Stamey) types. Such differences may have important implications for diagnosis and therapy. Evidence showing progression of ulcerative to nonulcerative disease, or vice versa, is lacking.

• #54 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  The hallmark of classic interstitial cystitis is a diffusely reddened appearance to the bladder surface epithelium associated with 1 or more ulcerative patches surrounded by mucosal congestion (ie, Hunner ulcer) on the dome or lateral walls of the bladder upon cystoscopic examination. […] The nonulcerative type of interstitial cystitis is characterized by similar clinical symptoms (ie, frequency, urgency, pelvic pain), but the cystoscopic findings noted for the ulcerative lesion are absent. Instead, after overdistention, these patients demonstrate glomerulations that are discreet, tiny, raspberry-like lesions appearing on the dome and lateral walls of the bladder and tiny mucosal tears and submucosal hemorrhages.

• #55 New Approaches in Managing Interstitial Cystitis/Bladder Pain Syndrome

  https://www.uspharmacist.com/article/new-approaches-in-managing-interstitial-cystitis-bladder-pain-syndrome

  The etiology and pathogenesis of IC/BPS is not well understood. There may be several factors leading to the manifestation of this disease, and several varying mechanisms have been proposed. Urothelial abnormalities have been found in IC/BPS cases, including an autoimmune or immunologic response causing altered bladder epithelial expression of specific antigens, alterations in the glycosaminoglycan (GAG) layer, and altered cytokeratin profile. The GAG layer helps protect the bladder from surface irritants, so if it is altered, irritants may leak from the urine into the bladder tissue, resulting in pain and inflammation. In some cases, the bladder wall is scarred or shows petechial hemorrhages known as glomerulations. In approximately 10% of IC/BPS cases, Hunner lesions or patches of broken skin on the bladder wall are present. […] Some information suggests that foods and beverages such as alcohol, caffeine, citrus fruits, tomatoes, and spicy foods may worsen symptoms; however, this is variable from patient to patient.

• #56 Interstitial Cystitis: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/2055505-overview

  The hallmark of classic interstitial cystitis is a diffusely reddened appearance to the bladder surface epithelium associated with 1 or more ulcerative patches surrounded by mucosal congestion (ie, Hunner ulcer) on the dome or lateral walls of the bladder upon cystoscopic examination. […] The nonulcerative type of interstitial cystitis is characterized by similar clinical symptoms (ie, frequency, urgency, pelvic pain), but the cystoscopic findings noted for the ulcerative lesion are absent. Instead, after overdistention, these patients demonstrate glomerulations that are discreet, tiny, raspberry-like lesions appearing on the dome and lateral walls of the bladder and tiny mucosal tears and submucosal hemorrhages.

• #57 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is multifactorial. Identifying the clinical characteristics and cystoscopic findings of bladder-centered IC/BPS facilitates optimal treatment strategies targeting the diseased urinary bladder. […] The known pathological findings from the bladders of IC/BPS patients included urothelial denudation, chronic inflammation, and sensory afferent activation. […] The prominent pathological findings of IC/BPS bladders include chronic inflammation and urothelial denudation. Inflammation is higher in bladders with Hunner’s lesions (HIC) compared with inflammation in non-Hunner’s IC (NHIC). […] The severity of bladder wall inflammation is highly associated with the severity of IC symptoms, glomerulation grade, and maximal bladder capacity under cystoscopic hydrodistention in bladder-centered IC/BPS patients, which indicates the pathological lesions are located inside the urinary bladder.

• #58 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  Increased microvascular endothelial cell apoptosis in IC bladders causes glomerulations, and impaired urothelial homeostasis is associated with chronic bladder inflammation. […] Chronic pain in patients with IC/BPS is likely caused by central nervous system (CNS) sensitization and activation of sensory afferent nerves. […] Bladder epithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult infection may also cause bladder pain. […] The treatment of IC/BPS should follow the possible pathophysiology and specific clinical presentation. Because the actual etiology and diagnosis of IC/BPS remain unclear, treatments usually target the pathogenesis, including the post-infection autoimmune process, mast cell activation, urothelial dysfunction, and neurogenic inflammation.

• #59 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #60 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #61 The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/12/9/2051

  Chronic inflammation in IC/BPS may be induced by toxins, bacterial infection, surgical trauma, autoimmune reactions, or systemic disorders. […] The pathogenesis of IC/BPS may involve an allergic reaction. […] The pathophysiology of IC/BPS includes chronic inflammation, viral infection, urothelial dysfunction, sensory nerve hyperplasia, lymphoplasmatic cell infiltration, chronic lymphoid follicle aggregation, bladder wall thickening, central nervous system sensitization, extravesical inflammation, and psychological stress.

• #62 Review of intravesical therapies for bladder pain syndrome/interstitial cystitis – Cvach – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8189/html

  Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic pain syndrome characterised by pain/discomfort attributed to the bladder, with associated urgency and urinary frequency. […] The underlying etiology of BPS/IC is not well understood and it is likely that a number of mechanisms play a role in the development of the condition. The urothelium/transitional epithelium is thought to play a fundamental role in the pathogenesis of BPS/IC. […] Once the subepithelial cells come into contact with urinary solutes, an inflammatory reaction is triggered, in turn resulting in decreased urothelial production of GAG and exacerbation of urothelial permeability and inflammation. Urothelial damage results in pathologic C-fiber activation, causing smooth muscle contraction, neurogenic inflammation, and hypersensitivity.

• #63 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #64 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #65 Pathophysiology of interstitial cystitis/bladder pain syndrome

  http://www.tzuchi.com.tw/medjnl/index.php/more-periodicals/153-2015/vol-27-4/518-pathophysiology-of-interstitial-cystitis-bladder-pain-syndrome

  A local inflammatory process might be induced through the afferent and efferent nerves in the suburothelial interstitial cellular network, which integrates the transmission of signals from the urothelium to the detrusor muscles in the bladder wall. […] Thus, the pathogenesis of IC might be involved in systemic disorders. […] It is possible to postulate that the pathophysiology of IC might evolve sequentially by: (1) urothelial injury (urinary tract infection, surgical trauma, chronic bladder overdistention); (2) suburothelial inflammation; (3) chronic inflammatory cell infiltration in the suburothelium; and (4) increased inflammatory reaction in the sensory afferents, dorsal horn ganglia, and corresponding spinal cord. […] The inflammatory reaction proceeds along the sensory nerves in the dorsal root ganglion as well as the sacral cord. […] If the insult does not continue, the inflammation resolves and patients may have symptom relief after symptomatic treatment. However, if the bladder insult continues, the inflammatory reaction increases to a higher level, causing permanent inflammation printing.

• #66 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #67 Interstitial Cystitis/Painful Bladder Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2011/0515/p1175.html

  Damaged urothelium produces cytokines that activate mast cells in the interstitium. […] The diffusion of excess potassium into the bladder interstitium through a defective urothelium also triggers mast cell activation. […] The activation of mast cells results in a cycle of neuronal hyperexcitability leading to secretion of neurotransmitters and triggering further mast cell stimulation and degranulation. This process appears to contribute to the chronic pain, urgency, and frequency experienced by patients. […] Several painful pelvic processes in men and women have demonstrated relationships to abnormalities in the urothelium, including chronic urethritis, chronic prostatitis, and chronic pelvic pain. On this basis, one expert has proposed renaming the group of conditions as lower urinary dysfunctional epithelium.

• #68 Interstitial Cystitis/Painful Bladder Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2011/0515/p1175.html

  Damaged urothelium produces cytokines that activate mast cells in the interstitium. […] The diffusion of excess potassium into the bladder interstitium through a defective urothelium also triggers mast cell activation. […] The activation of mast cells results in a cycle of neuronal hyperexcitability leading to secretion of neurotransmitters and triggering further mast cell stimulation and degranulation. This process appears to contribute to the chronic pain, urgency, and frequency experienced by patients. […] Several painful pelvic processes in men and women have demonstrated relationships to abnormalities in the urothelium, including chronic urethritis, chronic prostatitis, and chronic pelvic pain. On this basis, one expert has proposed renaming the group of conditions as lower urinary dysfunctional epithelium.

• #69

  https://discovery.ucl.ac.uk/id/eprint/10121271/

  Aberrant urothelial HLA-DR expression was found in all but one of the IC cases in which the urothelium was not denuded. […] Furthermore, the urothelium and submucosa in IC was infiltrated by CD4+, CD8+ and T cells, plasma cells, mast cells and macrophages. […] The precise aetiology of IC remains obscure although this study has revealed a genetic predisposition to the development of IC and has demonstrated immunological autoreactive mechanisms in the pathogenesis of this condition.

• #70 Bladder Pain Syndrome vs Interstitial Cystitis | Aare Urocare

  https://aareurology.sg/conditions/bladder-pain-syndrome-bps-vs-interstitial-cystitis-ic/

  The bladder urothelium is lined by glycosaminoglycans that help to prevent adherence of uropathogens to the urothelium. In addition, it protects the urothelium by being impermeable to various toxic solutes in the urine. It is possible that a disruption in the glycosaminoglycans layer could lead to interstitial cystitis. […] It is reported that the prevalence of interstitial cystitis in adult first-degree relatives of patients with the condition is 17 times higher than the normal population.

• #71 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://www.einj.org/journal/view.php?doi=10.5213/inj.1632712.356

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization.

• #72 Pathomechanism of Interstitial Cystitis/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease

  https://dspace.kci.go.kr/handle/kci/1146560

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. […] Different gene expressions have also been found in different IC phenotypes. […] Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease.

• #73 Interstitial Cystitis/Bladder Pain Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK570588/

  Other findings associated with chronic bladder inflammation include decreased mucosal protection from GAGs loss or dysfunction, lower adhesive protein E-cadherin, decreased basal cell growth, defective umbrella cell integrity, abnormal apical cell maturation, and increased urothelial cell apoptosis. […] The increased serum levels of C-reactive protein and pro-inflammatory cytokines also point to inflammation as a primary underlying etiology of IC/BPS. […] IC/BPS can appear as two separate entities: the IC entity clearly demonstrates an inflammatory component that is mostly missing in those with the predominantly BPS entity. […] Chronic stress is found in 50% of IC/BPS patients, which is a factor in the development and exacerbation of symptoms. […] The chronic pain typically associated with IC/BPS is caused by sensory afferent nerve activity and central nervous system sensitization.

• #74 Interstitial cystitis – Wikipedia

  https://en.wikipedia.org/wiki/Interstitial_cystitis

  Deficiency in this glycosaminoglycan layer on the surface of the bladder results in increased permeability of the underlying submucosal tissues. […] Numerous studies have noted the link between IC, anxiety, stress, hyper-responsiveness, panic, and abuse. […] Another proposed mechanism for interstitial cystitis is the autoimmune mechanism. […] Biopsies on the bladder walls of people with IC may contain mast cells. […] The activation of mast cells triggers the release of histamine, amongst other inflammatory mediators. […] Additionally, another proposed mechanism is increased activity of unspecified nerves in the bladder wall. […] An unknown toxin or stimuli may activate nerves within the bladder wall, causing the release of neuropeptides. These neuropeptides can induce a secondary cascade which stimulates pain in the bladder wall.

• #75 Interstitial Cystitis: Causes, Symptoms, Diagnosis & Treatment

  https://my.clevelandclinic.org/health/diseases/15735-interstitial-cystitis-painful-bladder-syndrome

  Stage 4 interstitial cystitis/bladder pain syndrome is when you have continuing IC/BPS symptoms for over two years. […] Your bladder tissue becomes very hard and cant hold as much pee. […] Interstitial cystitis/bladder pain syndrome symptoms vary. […] Symptoms include: Inflamed bladder (cystitis), Pain in your bladder region, Pressure or discomfort when your bladder is filling with pee, Peeing more often and feeling like you need to pee right away, Only peeing a small amount. […] Stress may trigger IC/BPS flare-ups. […] Nerve stimulation (neuromodulation therapy) regulates your bladder by reducing urgency and frequency. […] It may take several weeks or months before your symptoms start to improve after IC/BPS treatment.

• #76 Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/interstitial-cystitis-bladder-pain-syndrome-clinical-features-and-diagnosis

  Chronic bladder pain can be a debilitating condition that impacts quality of life. The pathophysiology of chronic bladder pain is not well understood, and symptoms likely represent more than one underlying etiology. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a diagnosis that applies to patients with chronic bladder pain in the absence of other explanatory etiologies. Identification of patients who meet diagnostic criteria for IC/BPS allows for treatment with the goal of providing symptomatic relief. This condition often coexists with other chronic pain syndromes (eg, fibromyalgia, irritable bowel syndrome). […] The pathogenesis, clinical features, and diagnosis of IC/BPS will be discussed here. Management of this condition is reviewed separately. Chronic bladder pain in the absence of an identifiable etiology has historically been called interstitial cystitis. This term is a misnomer, however, since there is no clear evidence that bladder inflammation (cystitis) is involved in the etiology or pathophysiology of the condition, nor is there evidence that the condition is reliably associated with abnormalities of the interstitium of the bladder.

• #77 Interstitial cystitis/bladder pain syndrome: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/interstitial-cystitis-bladder-pain-syndrome-clinical-features-and-diagnosis

  The understanding is that patients with these symptoms have a chronic pain condition of the bladder, analogous to other poorly understood chronic pain conditions such as fibromyalgia or irritable bowel syndrome. As such, the preferred nomenclature for this constellation of symptoms is painful bladder syndrome or bladder pain syndrome. However, considerable previous efforts have been devoted to recognizing „interstitial cystitis” as a legitimate, disabling medical condition and, therefore, the term has been retained in contemporary use to maintain continuity. This topic review uses the term „interstitial cystitis/bladder pain syndrome.”

• #78 :: International Neurourology Journal

  https://www.einj.org/m/journal/view.php?number=621

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. […] It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. […] Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. […] Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. […] The pathophysiology of IC/BPS might involve chronic inflammation, increased apoptosis, urothelial dysfunction, and CNS sensitization. […] The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS.

• #79 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #80 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #81 Review of intravesical therapies for bladder pain syndrome/interstitial cystitis – Cvach – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8189/html

  The rationale for the use of many of the currently used intravesical therapies is to replenish the deficient GAG layer or to alter the process of neurogenic inflammation and hypersensitivity. […] Heparin is a sulfonated GAG with the theoretical action of replenishing the urothelial GAG layer. […] PPS is the only oral agent approved for BPS/IC by the FDA. It is an oral heparinoid and likely exerts its effect in the treatment of BPS/IC by restoring the GAG layer. […] The rationale for using HA is to replenish deficiencies in the GAG layer although other biological activities including enhancement of connective tissue healing and inhibition of leukocyte migration and aggregation may contribute to its action in BPS/IC patients. […] CS is a component of the GAG layer and has been shown to be deficient in patients with BPS/IC. As well as its role in the GAG layer, CS has been shown to inhibit the recruitment of inflammatory cells to the deep layers of the bladder wall.

• #82 Review of intravesical therapies for bladder pain syndrome/interstitial cystitis – Cvach – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8189/html

  HA-CS has been shown to reduce the production of proinflammatory cytokines, reduce urothelial permeability, and facilitate the repair of the protective GAG layer. […] The exact mechanism of action of OS in BPS/IC is unclear but some have hypothesised that it may act by desensitising or degranulating bladder nociceptive nerve endings. […] Chronic inflammation and apoptotic signalling molecules is significantly reduced following intravesical botulinum toxin A injections, but only after repeated injections.

• #83 Current guidelines in the management of interstitial cystitis – Colaco – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8346/html

  Interstitial cystitis (IC), also referred to as bladder pain syndrome (BPS), is a heterogeneous chronic disease of unknown etiology that impacts up to 8 million women in America. […] Since Alexander Skenes inception of the term in 1887, research into the etiology and pathophysiology of this disease has not been successful in elucidating a specific mechanism, revealing more questions than answers. As a result, treatment is difficult. […] Hydroxyzine and cimetidine are an H1-receptor agonist and an H2-receptor antagonist, respectively. These drugs may affect IC by preventing mast cell degranulation and histamine release (one of the mechanisms that has been suggested in the pathophysiology of IC). […] PPS is a polysulfated xylan and the only FDA-approved oral medication to treat IC. This medication is thought to exert its effect by repairing the glycosaminoglycan (GAG) layer of the bladder urothelium and reducing its permeability. […] Although the pathophysiology of IC is still poorly understood, a wide number of treatment options are available depending on severity of symptoms.

• #84 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #85 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #86 Interstitial Cystitis/Painful Bladder Syndrome – The Urology Foundation

  https://www.theurologyfoundation.org/urology-health/bladder-conditions/5631-2/

  Nerve stimulation therapies – whilst sacral nerve stimulation (SNS) and tibial nerve stimulation (TNS) are more commonly used to treat overactive bladder (OAB) they can also be considered for the management of IC/PBS. […] The mechanism of these therapies, which involve ‘neuromodulation’ of bladder function, can potentially benefit patients with IC/PBS by reducing urinary urgency, frequency, and pelvic pain/discomfort.

• #87 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #88 Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome | Nature Reviews Urology

  https://www.nature.com/articles/s41585-023-00850-y

  Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. […] The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. […] Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. […] Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. […] However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. […] As IC/BPS might be multifactorial, future research should target different implicated pathways simultaneously and study the role of reactive oxygen species as a root cause in IC/BPS.

• #89 Etiology, Pathogenesis, and Diagnosis of Interstitial Cystitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476007/

  Substance P, a tachykinin released by activated C-fiber afferents, is involved in nociception in the central and peripheral nervous systems and also functions as an inflammatory mediator. […] Mast cells contain vasoactive and inflammatory mediators, and they play a central role in the pathogenesis of neuroinflammatory conditions, including IC. […] IC has many features of an autoimmune diseasechronicity, exacerbations and remissions, clinical response to steroids/immunosuppressives, the high prevalence of antinuclear antibodies, and association with other autoimmune syndromes. […] No single pathological process is universally present in IC. IC may well have multiple etiologies that result in the symptoms of irritative voiding and pain. Changes in urothelial permeability, sensory nerve stimulation, and mast cell activation are interrelated with multiple positive and negative feedback loops occurring simultaneously. […] The multifactorial etiology of IC and its complex, interrelated pathogenesis involving the bladder urothelium, sensory nerves, and mast cells are being increasingly defined.

• #90 Current Understanding of the Pathophysiology and Novel Treatments of Interstitial Cystitis/Bladder Pain Syndrome

  https://www.mdpi.com/2227-9059/10/10/2380

  Bladder dysfunction might originate from chronic inflammation, causing urothelial defects and more tissue reactions, subsequently leading to inflammation of the CNS. […] The fundamental pathophysiology of IC/BPS includes chronic bladder inflammation, increased urothelial cell apoptosis, decreased urothelial proliferation and differentiation, and defects in the urothelial barrier.

• #91 Interstitial cystitis – pathogenesis, diagnosis and treatment strategies: an update. part 1 – pathogenesis | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnosis-and-treatment-strategies-update-part-1-pathogen

  Interstitial cystitis/Bladder pain syndrome (IC/BPS) is the severe pathologic condition with strong impact on quality of life. Current treatment options are not completely effective as far as IC/BPS has very complex pathogenesis, which include such factors as: […] Urotheliums impairment […] Non-bacterial inflammation in the suburothelium with mast cells activation. […] Sensitization of peripheral nervous endings. […] Pelvic organs cross-talking. […] Pelvic floor muscles overactivity. […] Central sensitization. […] Thats why correct therapeutic strategies should involve all those factors.

• #92 Interstitial cystitis: pathogenesis, diagnostics and treatment (part 2) | Experimental and clinical urology

  https://ecuro.ru/en/article/interstitial-cystitis-pathogenesis-diagnostics-and-treatment-part-2

  This review summarizes the diagnostics and treatment of the main factors of pathogenesis of interstitial cystitis (IC)/painful bladder syndrome. […] The treatment of the damaged or incompetent glycosaminoglycan (GAG) layer of the urothelium includes cystoscopy combined with hydrodistention of the bladder followed by intracystic and oral GAG-replacement therapy. Abacterial inflammation of the interstitium followed by activation of mast cells is diagnosed by determining the level of cytokines in urine and by pathohistological examination of the urothelium; the treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids. […] The sensibilization of the peripheral nervous system due to the increase in the number of nociceptors is defined by determining the level of cytokines in urine and by immunohistochemical examination of the urothelium. The treatment includes intracystic instillations and irrigation of the bladder with a warm solution of anesthetics and glucocorticosteroids, and also injections of botulinic neuropeptide into the Lyeto triangle.

• #93 Current guidelines in the management of interstitial cystitis – Colaco – Translational Andrology and Urology

  https://tau.amegroups.org/article/view/8346/html

  Interstitial cystitis (IC), also referred to as bladder pain syndrome (BPS), is a heterogeneous chronic disease of unknown etiology that impacts up to 8 million women in America. […] Since Alexander Skenes inception of the term in 1887, research into the etiology and pathophysiology of this disease has not been successful in elucidating a specific mechanism, revealing more questions than answers. As a result, treatment is difficult. […] Hydroxyzine and cimetidine are an H1-receptor agonist and an H2-receptor antagonist, respectively. These drugs may affect IC by preventing mast cell degranulation and histamine release (one of the mechanisms that has been suggested in the pathophysiology of IC). […] PPS is a polysulfated xylan and the only FDA-approved oral medication to treat IC. This medication is thought to exert its effect by repairing the glycosaminoglycan (GAG) layer of the bladder urothelium and reducing its permeability. […] Although the pathophysiology of IC is still poorly understood, a wide number of treatment options are available depending on severity of symptoms.

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