Materiały źródłowe

• #1 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10932578/

  Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. […] A recent study also revealed that vibegron may have 2 mechanisms of action: inhibition of ACh from cholinergic efferent nerves in the detrusor and afferent inhibition via urothelial 3-AR. […] OAB pathophysiology has mostly been approached from 3 major perspectives. Neurogenic theory can be explained by degenerative changes or damages in the nerve pathway involved in the micturition reflex. Another perspective, the myogenic hypothesis, is that the changes in the muscle cells of the bladder may lead to bladder overactivity. More recently, the urothelial role in the changes of bladder afferent signaling pathway, which result in OAB, has been proposed. […] These stimuli, which fire spontaneously like a pacemaker, are also referred to as micromotion, spontaneous contraction, or afferent noises and are attracting attention as one of the causes of bladder overactivity.

• #2 Pathophysiology of Overactive Bladder and Urge Urinary Incontinence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476015/

  Storage symptoms such as urgency, frequency, and nocturia, with or without urge incontinence, are characterized as overactive bladder (OAB). OAB can lead to urge incontinence. Disturbances in nerves, smooth muscle, and urothelium can cause this condition. […] Models have been developed to mimic the OAB associated with bladder instability, lower urinary tract obstruction, neuropathic disorders, diabetes, and interstitial cystitis. These models share the common features of increased connectivity and excitability of both detrusor smooth muscle and nerves. Increased excitability and connectivity of nerves involved in micturition rely on growth factors that orchestrate neural plasticity. Neurotransmitters, prostaglandins, and growth factors, such as nerve growth factor, provide mechanisms for bidirectional communication between muscle or urothelium and nerve, leading to OAB with or without urge incontinence.

• #3

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  Evidence is mounting that poor bladder perfusion and local inflammatory responses are central mechanisms involved in the development of OAB/DO. […] Overactive bladder syndrome (OAB) is a set of storage symptoms that consists of urgency, frequency, nocturia, and urge urinary incontinence. The most common symptoms of OAB are urinary urgency and frequency and these may be associated with involuntary contractions of the detrusor smooth muscle (detrusor overactivity, DO). The most common cause of OAB is DO, which has been identified on cystometry in more than 60% of OAB patients. […] Most cases of OAB are idiopathic, with unknown pathophysiology, but several hypotheses have been proposed to explain this condition including: (i) A myogenic mechanism involving dysfunction of the detrusor smooth muscle resulting in spontaneous contractions. More recently changes in the initiation and propagation of microcontractions has been suggested.

• #4 Pathophysiology of Overactive Bladder | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-97265-7_1

  Overactive bladder (OAB) syndrome is defined by the International Continence Society as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence, in the absence of urinary tract infection or other obvious pathologies. […] Various theories have been proposed to elucidate the pathophysiology of OAB. However, since the cause of OAB is often multifactorial and complex, there is not a unique and widely accepted pathophysiological mechanism to explain this syndrome. […] This chapter aims to describe the various hypotheses, which may help in understanding the origin of OAB symptoms.

• #5 Overactive bladder – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/overactive-bladder/symptoms-causes/syc-20355715

  Overactive bladder happens when the muscles of the bladder start to tighten on their own even when the amount of urine in the bladder is low. These are called involuntary contractions. They cause an urgent need to urinate. […] Several conditions may be a part of overactive bladder, including: Conditions that affect the bladder, such as tumors or bladder stones. Conditions that affect the brain and spinal cord, such as stroke and multiple sclerosis. Diabetes. Factors that get in the way of urine leaving the bladder, such as an enlarged prostate, constipation or having had surgery to treat lack of control over urinating, called incontinence. Hormonal changes during menopause. Urinary tract infections, which can cause symptoms like those of an overactive bladder. […] Overactive bladder symptoms also may be linked to: Cognitive decline due to aging. This can make it harder for the bladder to use the signals it gets from the brain. Drinking too much caffeine or alcohol. Medicines that cause the body to make a lot of urine or that need to be taken with a lot of fluids. Not being able to get to the bathroom quickly. Not emptying the bladder all the way. This leads to not enough space in the bladder for more urine. […] Sometimes the cause of overactive bladder isn’t known.

• #6 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  http://einj.org/journal/view.php?doi=10.5213/inj.2448002.001

  Overactive bladder (OAB) is a symptom-based syndrome defined by urinary urgency, frequency, and nocturia with or without urge incontinence. The causative pathology is diverse; including bladder outlet obstruction (BOO), bladder ischemia, aging, metabolic syndrome, psychological stress, affective disorder, urinary microbiome, localized and systemic inflammatory responses, etc. Several hypotheses have been suggested as mechanisms of OAB generation; among them, neurogenic, myogenic, and urothelial mechanisms are well-known hypotheses. […] Neurogenic theory can be explained by degenerative changes or damages in the nerve pathway involved in the micturition reflex. Another perspective, the myogenic hypothesis, is that the changes in the muscle cells of the bladder may lead to bladder overactivity. More recently, the urothelial role in the changes of bladder afferent signaling pathway, which result in OAB, has been proposed. Other researchers have also focused on continuous stimulation transmitted from the bladder to the CNS, regardless of whether the source is nerve, muscle, or urothelium. These stimuli, which fire spontaneously like a pacemaker, are also referred to as micromotion, spontaneous contraction, or afferent noises and are attracting attention as one of the causes of bladder overactivity.

• #7 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  http://einj.org/journal/view.php?doi=10.5213/inj.2448002.001

  Neurogenic factors have 2 main causes. One is that the inhibitory system, which controls the micturition reflex, is damaged and does not work properly, and the other is that the micturition reflex is enhanced. […] The thalamus also seems to modulate the lower urinary tract function, and thalamic deep brain stimulation induced the urge to urinate earlier and decreased bladder capacity. […] In periphery, bladder afferents are located in the suburothelial layer and interact and participate in signal transmission through numerous excitatory and inhibitory transmitters released from the urothelium. Dysregulation of bladder afferent activity results in changes in micturition signals in the efferent pathway, resulting in detrusor dysfunction. […] Predisposing factors such as partial denervation and bladder ischemia may alter the properties of the detrusor smooth muscle, and DO may result from the histologic changes in the detrusor, which may result in spontaneous, autonomous cellular activity mediated by extracellular Ca2+ influx and intracellular Ca2+ release.

• #8 Overactive bladder syndrome: risk factors, diagnosis, management and medicine optimisation in older people – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/overactive-bladder-syndrome-risk-factors-diagnosis-management-and-medicine-optimisation-in-older-people

  The myogenic factor theory suggests that damaged intrinsic neurons in the bladder wall, along with secondary changes in smooth-muscle properties over time, may increase excitability and electrical coupling between cells. […] In the neurogenic factor theory, damage to central inhibitory pathways in the brain and spinal cord results in a loss of inhibitory effects and unmasks the early voiding reflexes that trigger detrusor overactivity. […] The urotheliogenic factor theory focuses on the role of the urothelium, which was previously considered mainly as a barrier but is now recognised as a responsive structure, capable of detecting thermal, mechanical and chemical stimuli.

• #9 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10932578/

  Neurogenic factors have 2 main causes. One is that the inhibitory system, which controls the micturition reflex, is damaged and does not work properly, and the other is that the micturition reflex is enhanced. […] Causes of enhancement of the micturition reflex include abnormally increased afferent activities from the bladder and increased excitatory neurotransmission from the CNS by neural remodeling. […] Predisposing factors such as partial denervation and bladder ischemia may alter the properties of the detrusor smooth muscle, and DO may result from the histologic changes in the detrusor, which may result in spontaneous, autonomous cellular activity mediated by extracellular Ca2+ influx and intracellular Ca2+ release. […] Coordinated myogenic contraction and increased intravesical pressure can then generate urgency by transferring afferent signals to the CNS.

• #10 Overactive Bladder: Practice Essentials, Background, Anatomy and Physiology

  https://emedicine.medscape.com/article/459340-overview

  Sensory afferent nerves may also play a role in OAB. Activation of normally quiescent C sensory fibers may help produce symptoms of OAB in individuals with neurologic and other disorders. Several types of receptors identified on sensory nerves may have a role in OAB symptoms. These include vanilloid, purinergic, neurokinin A, and nerve growth factor receptors. Substances such as nitric oxide, calcitonin gene-related protein, and brain-derived neurotropic factor may also have a role in modulating sensory afferent fibers in the human bladder. […] Once thought to be biologically inert, the urothelium may also have a role in OAB. The urothelium communicates directly with suburothelial afferents acting as luminal sensors. Low pH, high potassium concentration, and increased osmolality in the urine can influence sensory nerves. Activation of suburothelial afferent fibers without changes in the smooth muscle may lead to urgency. Activation of the suburothelial afferents in the presence of enhanced smooth-muscle coupling may lead to urgency and unstable detrusor contractions.

• #11 Pathophysiology of Overactive Bladder and Urge Urinary Incontinence

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1476015/

  The molecular trigger for changes in the afferents or synaptic transmission in the central nervous system (CNS) may be nerve growth factor (NGF), in addition to other neurotrophins (brain-derived neurotrophic factor, neurotrophins 3 and 4, glial-derived neurotrophic factor [GDNF]) and cytokines. NGF is responsible for the growth and maintenance of sympathetic and sensory neurons and has been shown to be responsible for neuronal regrowth after injury. NGF is elevated in the bladders of some models of OAB and in those of patients with BPH or IC and idiopathic detrusor instability. […] The urothelium directly communicates with suburothelial afferents acting as luminal sensors. Increased sensitivity of these afferents may lead to overactive bladder (OAB). […] Neuroplastic changes associated with OAB may result from alterations in activity in the nerves controlling the detrusor and probably involve nerve growth factor.

• #12 Volume 1, Chapter 88. The Overactive Bladder

  https://www.glowm.com/resources/glowm/cd/pages/v1/v1c088.html

  The pathophysiology of the overactive bladder is incompletely understood. However, to understand the currently proposed potential mechanisms, one must have a basic understanding of normal physiological bladder function. […] The bladder with overactivity appears to be both structurally and functionally altered. Within overactive bladder muscle, cell-to-cell junctions enable small foci of electronic activity to be propagated beyond their normal range, causing widespread smooth muscle contractions. […] It is clear that recent studies have helped to clarify the cause of inappropriate detrusor activity; however, much remains to be learned in this arena.

• #13 Overactive Bladder: Where We Are and Where We Are Going

  https://www.mdpi.com/2563-6499/2/5/311

  Overactive bladder (OAB) is a heterogeneous syndrome estimated to affect approximately 10% to 15% of men and women globally. […] Several etiologies for OAB have been defined: (1) myogenic detrusor overactivity (DO), (2) overactive signaling by the central nervous system (CNS) causing micturition (neurogenic), and (3) alterations within the urothelium of the lower urinary tract. […] The myogenic hypothesis attributes DO to changes within the bladder smooth muscle that result in increased excitability and spontaneous contraction. […] In the neurogenic hypothesis, bladder overactivity is attributed to increased neuroplasticity within the CNS. […] Two neurotrophins, specifically brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in OAB. […] Regarding the urothelial hypothesis, research in rat models indicates that chronic urothelial injury can cause increased urinary frequency and decreased voided volumes. […] Newer areas of exploration for OAB pathophysiology include the role of sex hormones, mood disorders, and the effect of the urinary microbiome.

• #14 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10932578/

  In the past, the urothelium was thought to be a simple barrier that isolates the bladder from the urine. However, more recently, it has been discovered that the urothelium is an important sensory organ that senses and communicates thermal, mechanical, and chemical stimuli beyond the passive barrier and plays an important immunological role in the pathogenesis of diseases such as OAB or interstitial cystitis/bladder pain syndrome (IC/BPS). […] Thus, spontaneous contractions from mucosa have been suggested as a possible cause of urgency. […] Pre- and postganglionic ACh from the parasympathetic nerve may be leaked from the parasympathetic nerves by bladder stretching, even during the normal storage phase. […] Although this local contraction is not coordinated and cannot increase intravesical pressure in all cases, it may generate an afferent signal, which triggers the micturition through the pontine micturition center, may eventually coordinate bladder contractions.

• #15 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  http://einj.org/journal/view.php?doi=10.5213/inj.2448002.001

  In the past, the urothelium was thought to be a simple barrier that isolate the bladder from the urine. However, more recently, it has been discovered that the urothelium is an important sensory organ that senses and communicates thermal, mechanical, and chemical stimuli beyond the passive barrier and plays an important immunological role in the pathogenesis of diseases such as OAB or interstitial cystitis/bladder pain syndrome (IC/BPS). […] Urothelial cells can be targets of transmitters secreted by nerves or other types of cells. It may also be activated through autocrine or paracrine mechanisms. Urothelium and suburothelium contain afferent nerves and receptors. During the storage phase, compounds produced and secreted here activate or inhibit the afferent pathway. […] Inflammation is not a common feature of OAB. However, Tyagi et al. reported that several markers related to inflammation were increased in the urine of OAB patients. […] Several hypotheses have been suggested for the mechanisms involved in OAB development, including those of neurogenic, myogenic, and urothelial origin; however, it is difficult to explain them using just one hypothesis as it seems that they are tangled and influence each other.

• #16

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  (ii) A neurogenic mechanism involving dysfunction of the central and/or peripheral nervous control of the bladder. A degeneration of nerves fibres within the bladder wall has been a defining feature of DO, with reductions in innervation observed in patients with idiopathic and neurogenic DO and in animal models of obstructive DO. […] (iii) More recently a pathological role for the urothelium has been proposed, with enhanced release of mediators such as ATP during bladder filling. Increased release of ATP from the urothelium during stretch has been observed in isolated bladder tissues from idiopathic and neurogenic OAB patients. […] Several factors linked to the development of OAB/DO are known to cause changes in bladder smooth muscle, neuronal and urothelial function. These include ageing, bladder outlet obstruction (BOO), obesity, psychological stress and undetected low level bacterial infections.

• #17

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  Ageing is thus associated with a number of factors that may accentuate the changes (eg inflammation) involved in the development of OAB/DO. […] Chronic BOO causes pathophysiological changes within all the layers of the bladder wall including detrusor hypertrophy, fibrosis, smooth muscle proliferation, urothelial dysfunction and a functional denervation. […] The powerful influence of stress on bladder function can also be demonstrated in animal models of environmental and social stress and both local changes in bladder function, and changes within the micturition pathways of the CNS and spinal cord have been identified. […] There is a well-established association between metabolic syndrome and OAB/DO in men, but this link can also be shown with other urological conditions such as BPH and erectile dysfunction.

• #18

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  A component of the definition of overactive bladder/detrusor is the absence of infection. However, in one study where antibiotics were administered to OAB patients who had tested negative for bacterial infection based on conventional urine bacterial levels symptoms improved in about half the patients. […] When the risk factors linked to OAB/DO are considered, inflammation and poor bladder blood flow stand out consistently. […] There is mounting evidence that ischemia of the bladder wall plays a role in the development of OAB/DO. […] The main causes of bladder wall ischemia are BOO and arterial occlusive disease, which reduce delivery of blood to the bladder microcirculation. […] Generally, reduced perfusion of tissues results in hypoxia and the accumulation of cellular metabolites. This in turn may enhance production of free radicals causing oxidative stress and the activation of inflammatory responses.

• #19

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  To examine the latest published findings on the pathophysiological mechanisms involved in the development of overactive bladder (OAB) and detrusor overactivity (DO), and to identify common pathways linked to the risk factors associated with these conditions. […] Evidence is accumulating, both clinical and experimental, that many of the factors linked to the development of OAB/DO, including ageing, bladder outlet obstruction, psychological stress, and obesity are associated with reduced bladder blood flow. This induces local tissue inflammation with cytokine release and enhanced oxidative stress, ultimately resulting in altered detrusor sensitivity, detrusor hypertrophy and fibrosis, together with afferent hypersensitivity. These mechanisms would explain the symptoms of urgency and frequency observed in OAB patients.

• #20

  https://link.springer.com/article/10.1007/s11884-023-00690-x

  Inflammation is a common feature of OAB/DO which may develop when bladder blood flow is reduced, or the bladder is stressed mechanically by BOO, or directly during infection. […] Thus, the mucosa is particularly susceptible to ischemic damage and inflammation. Since the mucosa contains many suburothelial afferent nerves and it also influences muscle contraction and afferent nerve activity via the mediators it releases, changes in blood flow to this region may have a huge impact on bladder function, even if other regions remain relatively well perfused. […] As our understanding if these mechanisms increases, the opportunity for novel drug development will also improve.

• #21 Medicinal plants and natural products for treating overactive bladder | Chinese Medicine | Full Text

  https://cmjournal.biomedcentral.com/articles/10.1186/s13020-024-00884-3

  The urotheliogenic hypothesis refers to dysfunctions in signal molecules and ion channels within the urothelium. The urothelium not only acts as a protective barrier but also functions as a sensor to thermal, mechanical, and chemical stimuli. In the absence of a healthy urothelium, there may occur an elevation in spontaneous detrusor activity. […] The myogenic hypothesis posits that impaired function of the myocytes in the detrusor muscle may cause elevated excitability, hence leading to the occurrence of uncontrolled contractions. […] The neurogenic hypothesis considers the abnormal management of afferent signals. In this case, urgency originates from the brain and spinal cord or peripheral afferent terminals in the bladder. […] The integrative hypothesis includes each of the above hypotheses since each of the components is likely to contribute to the pathophysiology of OAB considering the sophistication of mechanisms involved in micturition. Various potential triggers could induce local contractions (micromotions) in detrusor which are then transmitted to the bladder wall, resulting in occurrence of the sense of urgency.

• #22 2. Pathophysiology and Pharmacotherapy of Overactive Bladder

  https://www.jstage.jst.go.jp/article/jscpt/40/5/40_5_201/_article/-char/en

  Overactive bladder (OAB) syndrome, which is characterized by a complex of storage symptoms (urinary urgency, frequency, nocturia and urgency incontinence) is highly prevalent in the general population; it causes significant distress to patients in terms of their psychosocial and physical functioning. […] Muscarinic receptors of bladder smooth muscles are involved in both normal and involuntary detrusor contraction (detrusor overactivity). Up-regulation of the muscarinic receptor function may contribute to the pathophysiology of OAB. […] In addition, several reports have suggested that various stimulations release many substances (ATP, prostaglandins, nitric oxide and acetylcholine) from bladder urothelium, which contribute to the pathophysiology of the increased bladder sensation, OAB symptoms and detrusor overactivity.

• #23 Overactive Bladder: Practice Essentials, Background, Anatomy and Physiology

  https://emedicine.medscape.com/article/459340-overview

  OAB appears to be multifactorial in both etiology and pathophysiology. Symptoms of OAB are suggestive of underlying detrusor overactivity. Overactivity of the detrusor muscle—neurogenic, myogenic, or idiopathic in origin—may result in urinary urgency and urgency incontinence. […] The role of the M2 muscarinic receptor subtype in the human bladder is not well established. Data from small studies demonstrating up-regulation of the M2 receptor in certain pathologic states suggest that it may have a role in detrusor overactivity related to obstruction and spinal cord injury. […] Binding of acetylcholine to the M3 receptor activates phospholipase C via coupling with G proteins. This action causes the release of calcium from the sarcoplasmic reticulum and contraction of the bladder smooth muscle. Increased sensitivity to stimulation by muscarinic receptors may lead to OAB. Leakage of acetylcholine from the parasympathetic nerve terminal may lead to micromotion of the detrusor, which may activate sensory afferent fibers, leading to the sensation of urgency.

• #24 Lesson: Managing Overactive Bladder Syndrome

  https://journalce.powerpak.com/ce/managing-overactive-bladder-in-syndrome

  Detrusor muscle contraction is essential for normal micturition; however, abnormalities associated with detrusor muscle hyperactivity can produce many of the symptoms observed in patients with OAB. The cholinergic (parasympathetic) system is involved with detrusor muscle contraction and bladder emptying, and the adrenergic (sympathetic) system is involved with relaxation of the bladder muscle and contraction of the sphincters that assist in bladder filling and continence. While both M2 and M3 receptors are found in the detrusor muscle of the bladder, the M3 muscarinic receptor subtype is thought to be the most important in regulating detrusor contraction and voiding. The detrusor muscle also has -3 receptors that are involved with detrusor muscle relaxation and increased filling capacity of the bladder. Patients with hyperactivity of the detrusor muscle may have neurogenic and/or myogenic origins, but to date the cause of detrusor muscle hyperactivity is largely unknown.

• #25 Mechanism of Action | MYRBETRIQ® (mirabegron ER tablets)

  https://www.myrbetriqhcp.com/mechanism-of-action/

  Overactive bladder (OAB) is characterized by involuntary contraction of the detrusor muscle during the storage phase. […] Myrbetriq relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of the 3-AR. […] Mirabegron is an agonist of the human 3-AR as demonstrated by in vitro laboratory experiments using the cloned human 3-AR. […] Although mirabegron showed very low intrinsic activity for cloned human 1-AR and 2-AR, results in humans indicate that 1-AR stimulation occurred at a dose of 200 mg. […] MYRBETRIQ (mirabegron extended-release tablets), either alone or in combination with the muscarinic antagonist solifenacin succinate, is indicated for the treatment of overactive bladder (OAB) in adult patients with symptoms of urge urinary incontinence, urgency, and urinary frequency. […] In patients taking MYRBETRIQ, urinary retention has been reported in patients with bladder outlet obstruction (BOO) and in patients taking muscarinic antagonist medications for the treatment of OAB.

• #26 Relationship between the systemic immune-inflammatory index and overactive bladder risk: A cross-sectional assessment involving United States Adults | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0323052

  This study aimed to evaluate the association between the systemic immune-inflammatory index (SII) and the risk of overactive bladder (OAB) in the adult United States population. […] The primary pathological mechanism in OAB is detrusor overactivity, whereas other forms of urethrabladder dysfunction constitute a relatively small proportion of cases. […] Emerging evidence suggests a strong association between OAB and various risk factors, including obesity, smoking, alcohol consumption, physical inactivity, diabetes mellitus (DM), depression, and lower socioeconomic status. […] The immune system plays a critical role in the pathogenesis of numerous diseases, and accumulating research indicates that chronic, rather than acute, inflammation contributes to OAB development. […] Additionally, urinary chemokines such as monocyte chemotactic protein-1 and inflammatory proteins are significantly elevated in OAB patients compared to healthy controls, reinforcing the notion that chronic inflammation is a key feature of OAB pathophysiology.

• #27 Relationship between the systemic immune-inflammatory index and overactive bladder risk: A cross-sectional assessment involving United States Adults | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0323052

  The systemic immune-inflammatory index (SII) was initially introduced as a prognostic marker for conditions such as cancer, intracerebral hemorrhage, and coronary stenosis. […] However, to date, no consensus has been reached regarding the influence of SII on OAB, and only limited studies have investigated its prognostic value in OAB patients. […] A significantly positive association was observed between elevated SII and increased OAB risk when SII exceeded 3.40. […] These findings suggest that the combined assessment of peripheral neutrophil, lymphocyte, and platelet counts may facilitate the early identification of high-risk individuals predisposed to OAB, enabling timely interventions to mitigate disease development. […] The significant association between higher SII and OAB risk, particularly among individuals with comorbid conditions such as diabetes, hypertension, and chronic kidney disease, aligns with previous studies suggesting that chronic inflammation may disrupt bladder control mechanisms.

• #28 A brief physiology and pathophysiology of the bladder

  https://atm.amegroups.org/article/view/123658/html

  The remit of this review is confined to experimental works and publications relevant to the integral theory of female urinary incontinence (IT). Since its first publication in 1990, the IT has challenged the general view that the pathogenesis of overactive bladder (OAB) (urge, frequency, nocturia) is unknown and there is no cure. […] The pathogenesis of female urinary incontinence is from outside the bladder, mainly weak ligaments or vagina, due to collagen deficiency. […] Weak ligaments are an important cause of SUI, urgency (OAB), and emptying dysfunctions [underactive bladder (UAB)]. […] OAB is a prematurely activated but otherwise normal micturition. […] The integral theory paradigm (ITP)s main focus is loose or weak ligaments caused by altered collagen. Pathogenesis can be congenital, pregnancy/childbirth related or menopausal (collagen breakdown/excretion).

• #29 Pathogenesis of overactive bladder and surgical treatment according to the Integral Theory Paradigm | Gynecology and Obstetrics Clinical Medicine

  https://bibliotheek.ehb.be:2656/content/1/2/55#!

  Overactive bladder (OAB is a definition by the International Continence Society (ICS). It comprises three symptoms, urge, frequency and nocturia. OAB is generally assumed to be a paradigm, but it cannot meet the criteria of a paradigm, as its causation is said to be idiopathic (unknown) and is said to have no known treatment. The Integral Theory paradigm’s view of OAB is based on and is compatible with, ICS definitions and descriptions. The Integral Theory paradigm (ITP) views OAB pathogenesis as anatomical, caused by defects anywhere along the control mechanism pathway, but mainly damage in its weakest link, collagen defects in the peripheral musculoligamentous system. […] The pathogenesis of OAB is unknown, investigation by urodynamics has only a 50% diagnostic rate, and there is no known cure. The very name OAB is inappropriate, as it implies that the cause is within the detrusor itself.

• #30 Pathogenesis of overactive bladder and surgical treatment according to the Integral Theory Paradigm | Gynecology and Obstetrics Clinical Medicine

  https://bibliotheek.ehb.be:2656/content/1/2/55

  The Integral Theory paradigm states that any anatomical defect may cause OAB: cortical, spinal, peripheral nerves, inflammation, cancer or inflammation at bladder base (N), damaged ligaments, damaged muscles. However, a 35-year experience by the author indicates that idiopathic OAB, no known cause, at least in females, is mainly caused by loose ligaments weakening the muscle forces which close and open the urethra (Fig. 1A). […] The proofs of the Integral Theory’s paradigm that urge, frequency, nocturia (OAB) are an uncontrolled micturition governed by a feedback process were in fact based on ICS definitions and descriptions and do not conflict with ICS definitions, current or otherwise. […] The pathogenesis of PFS symptoms is summarized in Fig. 1 and 2. A key prediction of the Integral Theory, the presence of stretch/pressure receptors remained controversial until the early 2000s. […] Inability of either the front or back reflex muscle forces to tension the bladder base sufficiently to support the stretch/pain receptors allows excess afferents from N to reach the cortex and activate the micturition reflex. This is perceived as urge symptoms.

• #31 Pathophysiology of Overactive Bladder and Pharmacologic Treatments Including β3-Adrenoceptor Agonists -Basic Research Perspectives-

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10932578/

  Several hypotheses have been suggested for the mechanisms involved in OAB development, including those of neurogenic, myogenic, and urothelial origin; however, it is difficult to explain them using just one hypothesis as it seems that they are tangled and influence each other. […] If continued clinical and basic research increases our understandings of the action mechanisms in OAB medications including 3-AR agonists, better treatment approaches can be achieved to implement the pathogenesis-oriented therapy for OAB patients who do not respond to or have little effects by conventional treatments.

• #32 Frontiers | Overactive Bladder Symptoms Within Nervous System: A Focus on Etiology

  https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.747144/full

  Overactive bladder (OAB) is a common debilitating condition characterized by urgency symptoms with detrimental effects on the quality of life and survival. The exact etiology of OAB is still enigmatic, and none of therapeutic approaches seems curative. […] The OAB symptoms in neurological diseases are often poorly recognized and inadequately treated. This review provided a comprehensive overview of recent findings related to the neurogenic OAB symptoms. […] The pathophysiology of OAB symptoms in neurological diseases appears to be multifactorial across all levels of neural control of micturition, from cerebral cortex, brain stem, spinal cord, to the peripheral nerves. The site and nature of the neurological lesions may affect the appearing time, progression, and severity of OAB symptoms. A better knowledge of the neural component of normal micturition appears to be necessary to the role of neurological diseases in the etiology of OAB symptoms.

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