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Neurourology and Urodynamics 2010The coordination of pelvic physiologic function requires complex integrative sensory pathways that may converge both peripherally and/or centrally. Following a focal,... (Review)
Review
The coordination of pelvic physiologic function requires complex integrative sensory pathways that may converge both peripherally and/or centrally. Following a focal, acute irritative or infectious pelvic insult, these same afferent pathways may produce generalized pelvic sensitization or cross-sensitization as we show bi-directionally for the bladder and bowel in an animal model. Single unit bladder afferent recordings following intracolonic irritation reveal direct sensitization to both chemical and mechanical stimuli that's dependent upon both intact bladder sensory (C-fiber) innervation and neuropeptide content. Concurrent mastocytosis (preponderantly neurogenic) likely plays a role in long-term pelvic organ sensitization via the release of nociceptive and afferent-modulating molecules. Prolonged pelvic sensitization as mediated by these convergent and antidromic reflexive pathway may likewise lead to chronic pelvic pain and thus the overlap of chronic pelvic pain disorders.
Topics: Action Potentials; Afferent Pathways; Animals; Chronic Disease; Colon; Cystitis, Interstitial; Disease Models, Animal; Humans; Mast Cells; Mechanotransduction, Cellular; Nerve Fibers, Unmyelinated; Neurons, Afferent; Neuropeptides; Pelvic Pain; Sensation; Urinary Bladder
PubMed: 20025032
DOI: 10.1002/nau.20817 -
PloS One 2021Interstitial cystitis/bladder pain syndrome (IC/BPS) is not only a chronic urinary bladder pain syndrome but is also associated with multifactorial etiology. Our study...
Interstitial cystitis/bladder pain syndrome (IC/BPS) is not only a chronic urinary bladder pain syndrome but is also associated with multifactorial etiology. Our study aimed to test the hypothesis that IC/BPS is associated with subsequent increased risks of outpatient visits and hospitalizations. Using nationwide database, the diagnoses were based on the International Classification Codes (ICD-9-CM) (595.1) of at least three outpatient services during 2002-2008, (n = 27,990) and cystoscopic finding Hunner type and/or glomerulation with pre-audit criteria. All recruited cases monitored for subsequent outpatient visits and hospitalizations for 2 years, including all-cause and specialty-specific departments, were classified according to medical specialty and age group (<40, 40-60, ≥60 years of age). IC/BPS patients have more overall outpatient department (OPD) visits and an overall adjusted incidence rate ratio (IRR) of 1.64. As for specialty, IRRs were higher in psychiatry (2.75), Chinese medicine (2.01), and emergency medicine (2.00), besides urology and gynecology. The IRRs decreased as age advanced (2.01, 1.71, and 1.44, respectively), except for gynecology (2.42, 2.52, and 2.81). A similar phenomenon happens in hospitalization with IRR of 1.69. Due to claim data characteristics, whether ulcer type IC/BPS findings can be deductive to non-ulcer type remains inclusive. Current results indicate the impacts of healthcare burden in broad spectrum about IC/PBS patients. IC/BPS has been suggested to be associated with lower threshold of healthcare visits and some coexisting disease and is comprised of systemic dysregulation, and is beyond the scope of local bladder-urethra disease. Adequate recognition of associated or comorbid factors and possible recommendation or referral for IC/BPS patients can help provide better healthcare quality.
Topics: Abdominal Pain; Adult; Ambulatory Care; Cystitis, Interstitial; Data Management; Female; Hospitalization; Humans; Male; Middle Aged; Pelvic Pain; Risk Factors; Ulcer; Urinary Bladder
PubMed: 34492065
DOI: 10.1371/journal.pone.0256800 -
Urology Dec 2021To further examine anesthetic bladder capacity as a biomarker for interstitial cystitis/bladder pain syndrome (IC/BPS) patient subtypes, we evaluated demographic and...
OBJECTIVE
To further examine anesthetic bladder capacity as a biomarker for interstitial cystitis/bladder pain syndrome (IC/BPS) patient subtypes, we evaluated demographic and clinical characteristics in a large and heterogeneous female patient cohort.
MATERIAL AND METHODS
This is a retrospective review of data from women (n = 257) diagnosed with IC/BPS who were undergoing therapeutic bladder hydrodistention (HOD). Assessments included medical history and physical examination, validated questionnaire scores, and anesthetic BC. Linear regression analyses were computed to model the relationship between anesthetic BC and patient demographic data, symptoms, and diagnoses. Variables exhibiting suggestive correlations (P ≤ .1) were candidates for a multiple linear regression analysis and were retained if significant (P ≤ .05).
RESULTS
Multiple regression analysis identified a positive correlation between BC and endometriosis (P = .028) as well as negative correlations between BC and both ICSI score (P < .001) and the presence of Hunner's lesions (P < .001). There were higher average numbers of pelvic pain syndrome (PPS) diagnoses (P = .006) and neurologic, autoimmune, or systemic pain (NASP) diagnoses (P = .003) in IC/BPS patients with a non-low BC, but no statistical difference in the duration of diagnosis between patients with low and non-low BC (P = .118).
CONCLUSION
These data, generated from a large IC/BPS patient cohort, provide additional evidence that higher BC correlates with higher numbers of non-bladder-centric syndromes while lower BC correlates more closely with bladder-specific pathology. Taken together, the results support the concept of clinical subgroups in IC/BPS.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anesthetics; Autoimmune Diseases; Biomarkers; Cystitis, Interstitial; Endometriosis; Female; Humans; Lower Urinary Tract Symptoms; Middle Aged; Nervous System Diseases; Organ Size; Pelvic Pain; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Syndrome; Time Factors; Urinary Bladder; Young Adult
PubMed: 34303757
DOI: 10.1016/j.urology.2021.07.009 -
Molecular Neurobiology Feb 2019The periaqueductal gray matter (PAG), as one of the mostly preserved evolutionary components of the brain, is an axial structure modulating various important functions... (Review)
Review
The periaqueductal gray matter (PAG), as one of the mostly preserved evolutionary components of the brain, is an axial structure modulating various important functions of the organism, including autonomic, behavioral, pain, and micturition control. It has a critical role in urinary bladder physiology, with respect to storage and voiding of urine. The PAG has a columnar composition and has extensive connections with its cranially and caudally located components of the central nervous system (CNS). The PAG serves as the control tower of the detrusor and sphincter contractions. It serves as a bridge between the evolutionary higher decision-making brain centers and the lower centers responsible for reflexive micturition. Glutamatergic cells are the main operational neurons in the vlPAG, responsible for the reception and relay of the signals emerging from the bladder, to related brain centers. Functional imaging studies made it possible to clarify the activity of the PAG in voiding and filling phases of micturition, and its connections with various brain centers in living humans. The PAG may be affected in a wide spectrum of disorders, including multiple sclerosis (MS), migraine, stroke, Wernicke's encephalopathy, and idiopathic normal pressure hydrocephalus, all of which may have voiding dysfunction or incontinence, in certain stages of the disease. This emphasizes the importance of this structure for the basic understanding of voiding and storage disorders and makes it a potential candidate for diagnostic and therapeutic interventions.
Topics: Brain; Humans; Neural Pathways; Periaqueductal Gray; Urinary Bladder; Urinary Tract; Urinary Tract Physiological Phenomena
PubMed: 29804231
DOI: 10.1007/s12035-018-1131-8 -
Biochimica Et Biophysica Acta Aug 2007This review attempts to provide an overview of the current knowledge of TRP proteins and their possible role in bladder function and disease. At present, there are 28... (Review)
Review
This review attempts to provide an overview of the current knowledge of TRP proteins and their possible role in bladder function and disease. At present, there are 28 transient receptor potential (TRP) channels (subdivided into 7 categories or families) which are involved in a number of functions [G.A. Hicks, TRP channels as therapeutic targets: hot property, or time to cool down? Neurogastroenterology and Motility 18, (2006) 590-594., J.D. Levine, N. Alessandri-Haber, TRP channels: targets for the relief of pain, Biochimica et Biophysica Acta 1772, (2007) 989-1003.]. Of those belonging to the group 1 subfamily, a number of TRPV, TRPM and TRPA proteins associated with osmoregulation, thermal, chemical and mechanical signaling mechanisms have been shown to be expressed within the lower urinary tract. Though the biological role of many of these channels in urinary bladder function still remains elusive, TRPV1 is by far the best characterized and is thought to be involved in a number of bladder disorders [A. Szallasi, P.M. Blumberg, Vanilloid (Capsaicin) Receptors and Mechanisms, Pharmacological Reviews 51, (1999) 150-221., I. Nagy, P. Santha, G. Jansco, L. Urban, The role of the vanilloid (capsaicin) receptor (TRPV1) in physiology and pathology, European Journal of Pharmacology 500, (2004) 351-369.].
Topics: Animals; Gene Expression Regulation; Humans; Models, Biological; Transient Receptor Potential Channels; Urinary Bladder; Urinary Bladder Diseases
PubMed: 17560087
DOI: 10.1016/j.bbadis.2007.04.003 -
American Journal of Physiology.... Jun 2014Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or... (Review)
Review
Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered.
Topics: Adenosine Triphosphate; Animals; Disease Models, Animal; Humans; Mice; Nerve Growth Factors; Neuronal Plasticity; Neuropeptides; Sensory Receptor Cells; Urinary Bladder; Urinary Bladder Diseases; Urination
PubMed: 24760999
DOI: 10.1152/ajpregu.00030.2014 -
Lower Urinary Tract Symptoms Apr 2021Abdominal electromyogram or visceromotor response (VMR) elicited by bladder distension is a validated as a measure of bladder nociception in mice, however it is not...
OBJECTIVES
Abdominal electromyogram or visceromotor response (VMR) elicited by bladder distension is a validated as a measure of bladder nociception in mice, however it is not without its limitations. The aim of this study is to address some of these limitations and validate voiding evoked VMR as a measure of bladder nociception mice.
METHODS
Using both male and female C57BL/6 mice we assessed the VMR response to cytometry- induced voiding before and after instillation of 0.5% acetic acid into the bladder. We then delivered intravesical lidocaine to confirm the VMR response as nociceptive. VMR and correlative cystometric bladder pressures were analyzed.
RESULTS
We found that the VMR can be evoked by continuous fluid infusion into the bladder of both male and female mice. This response is potentiated after bladder injury and can be attenuated by administration of a local anesthetic, providing strong evidence that this method can be used to evaluate bladder nociception. Further, evaluation of cystometric pressure traces obtained during VMR recording revealed that intercontraction intervals were not altered after bladder injury in either male or female mice. However, we did observe a decrease in peak threshold pressures after bladder injury in female mice, which could be rescued by lidocaine administration.
CONCLUSIONS
In conclusion, this technique can measure the VMR and bladder nociception associated with voiding in both female and male mice. Although confounds still exist with the use of anesthesia, further exploration of non-anesthetized voiding-evoked VMR is warranted.
Topics: Animals; Female; Male; Mice; Mice, Inbred C57BL; Nociception; Urinary Bladder; Urination; Urodynamics
PubMed: 33202486
DOI: 10.1111/luts.12365 -
Pain Jan 2022Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that...
Excess pain after visceral provocation has been suggested as a marker for chronic pelvic pain risk in women. However, few noninvasive tests have been validated that could be performed readily on youth in early risk windows. Therefore, we evaluated the validity and reliability of a noninvasive bladder pain test in 124 healthy premenarchal females (median age 11, [interquartile range 11-12]), as previously studied in adult women. We explored whether psychosocial, sensory factors, and quantitative sensory test results were associated with provoked bladder pain and assessed the relation of bladder pain with abdominal pain history. Compared with findings in young adult females (age 21 [20-28]), results were similar except that adolescents had more pain at first sensation to void (P = 0.005) and lower maximum tolerance volume (P < 0.001). Anxiety, depression, somatic symptoms, and pain catastrophizing predicted provoked bladder pain (P's < 0.05). Bladder pain inversely correlated with pressure pain thresholds (r = -0.25, P < 0.05), but not with cold pressor pain or conditioned pain modulation effectiveness. Bladder pain was also associated with frequency of abdominal pain symptoms (r = 0.25, P = 0.039). We found strong retest reliability for bladder pain at standard levels of sensory urgency in 21 adolescents who attended repeat visits at 6 to 12 months (intraclass correlations = 0.88-0.90). Noninvasive bladder pain testing seems reproducible in adolescent females and may predict abdominal pain symptomatology. Confirmation of our findings and further investigation of the bladder test across menarche will help establish how visceral sensitivity contributes to the early trajectory of pelvic pain risk.
Topics: Adolescent; Adult; Child; Chronic Pain; Female; Humans; Pain Threshold; Pelvic Pain; Reproducibility of Results; Urinary Bladder; Young Adult
PubMed: 34086630
DOI: 10.1097/j.pain.0000000000002311 -
Neurourology and Urodynamics Apr 2023The prevalence of healthy bladder storage and emptying function in community-dwelling women is not well established.
INTRODUCTION
The prevalence of healthy bladder storage and emptying function in community-dwelling women is not well established.
METHODS
A planned secondary analysis of a US cross-sectional study designed to validate a bladder health instrument was conducted in women aged ≥18 years. A subset was invited to complete the novel 2-day bladder health diary capturing bladder storage and emptying experiences. Overall healthy bladder function was defined as ≤8 waking/daytime voids and ≤1 void during sleeping/nighttime; along with the absence of leakage, urgency, emptying difficulties (initiation, flow, efficacy, relief of urge sensation) and pain. Descriptive statistics of healthy bladder functions and regression models of factors associated with healthy function are reported.
RESULTS
Of the 383 invited, 237 (62%) eligible women returned complete dairies. Of these, 12% (29/237) met criteria for overall healthy bladder function. Most (96%) denied pain, 74% had healthy daytime and 83% had healthy nighttime voiding frequency, 64% were continent, 36% reported healthy emptying and 30% denied any urgency episodes. Middle income (odds ratio [OR]:95% confidence interval [CI] = 11.4:1.9-67.4 for $75k-$99 999 vs. $25 000-$49 999), Graduate education (4.8:1.4-17) and previously seeking treatment for bladder problems (OR:95%CI = 0.1; 0-0.9) were associated with overall healthy function.
CONCLUSION
The prevalence of overall healthy bladder function was very low based on our strict definition of health as measured on a 2-day diary. However, most women had healthy voiding frequency and denied pain or urinary leakage. Postvoid dribbling and urgency most commonly contributed to an overall unhealthy bladder. Further investigation is needed to determine whether these diary derived measures are meaningful for patient-oriented bladder health research.
Topics: Humans; Female; Adolescent; Adult; Urinary Bladder; Independent Living; Cross-Sectional Studies; Medical Records; Nocturia; Pain
PubMed: 36891924
DOI: 10.1002/nau.25169 -
World Journal of Gastroenterology Dec 2022Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory...
BACKGROUND
Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood.
AIM
To develop a model of chronic bladder-colon cross-sensitization and to investigate the mech-anisms involved.
METHODS
Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia. Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distensions. Myeloperoxidase, used as a marker of colorectal inflammation, was measured in the colon, and colorectal permeability was measured using chambers. c-Fos protein expression, used as a marker of neuronal activation, was assessed in the spinal cord (L6-S1 level) using immunohistochemistry. Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord. The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot.
RESULTS
Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid saline ( < 0.0001). This effect started 1 h post-injection and lasted up to 7 d post-injection. No increased permeability or inflammation was shown in the bladder or colon 7 d post-injection. Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord ( < 0.0001). In green fluorescent protein on the fractalkine receptor-positive mice, intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord ( < 0.0001). NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection ( = 0.007 and 0.023 respectively). Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline, a microglia inhibitor, by intracerebroventricular injection of CP-99994 dihydrochloride, a NK1 antagonist, and by intracerebroventricular injection of SB203580, a MAPK-p38 inhibitor.
CONCLUSION
We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice. Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension, mediated by neuroglial interactions, MAPK-p38 phosphorylation and the NK1 receptor.
Topics: Animals; Male; Mice; Rats; CX3C Chemokine Receptor 1; Green Fluorescent Proteins; Inflammation; Mice, Inbred C57BL; Proto-Oncogene Proteins c-fos; Rats, Sprague-Dawley; Spinal Cord; Urinary Bladder; Visceral Pain; Colon; Hyperalgesia; Chronic Pain; Microglia
PubMed: 36632316
DOI: 10.3748/wjg.v28.i48.6935