Neurobiology and long-term impact of bladder-filling pain in humans: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research network study.

ABSTRACT: Pain with bladder filling remains an unexplained clinical presentation with limited treatment options. Here, we aim to establish the clinical significance of bladder filling pain using a standardized test and the associated neural signature. We studied individuals diagnosed with urologic chronic pelvic pain syndrome (UCPPS) recruited as part of the multidisciplinary approach to the study of chronic pelvic pain (MAPP) study. Patients with urologic chronic pelvic pain syndrome (N = 429) and pain-free controls (N = 72) underwent a test in which they consumed 350 mL of water and then reported pain across an hour-long period at baseline and 6 months. We used latent class trajectory models of these pain ratings to define UCPPS subtypes at both baseline and 6 months. Magnetic resonance imaging of the brain postconsumption was used to examine neurobiologic differences between the subtypes. Healthcare utilization and symptom flare-ups were assessed over the following 18 months. Two distinct UCPPS subtypes were identified, one showing substantial pain related to bladder filling and another with little to no pain throughout the test. These distinct subtypes were seen at both baseline and 6 month timepoints. The UCPPS subtype with bladder-filling pain (BFP+) had altered morphology and increased functional activity in brain areas involved in sensory and pain processing. Bladder-filling pain positive status predicted increased symptom flare-ups and healthcare utilization over the subsequent 18 months when controlling for symptom severity and a self-reported history of bladder-filling pain. These results both highlight the importance of assessing bladder filling pain in heterogeneous populations and demonstrate that persistent bladder-filling pain profoundly affects the brain.

Immune cell profiles of patients with interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a disorder characterized by bladder pain upon filling which severely affects quality of life. Clinical presentation can vary. Local inflammatory events typify the clinical presentation of IC/BPS patients with Hunner lesions (IC/BPS-HL). It has previously been proposed that B cells are more prevalent in HL, but understanding their exact role in this environment requires a more complete immunological profile of HL. We characterized immunological dysfunction specifically in HL using immunohistochemistry. We detected significantly more plasma cells (50× increase, p < 0.0001), B cells (28× increase, p < 0.0001), T cells (3× increase, p < 0.0001), monocytes/macrophages (6× increase, p < 0.0001), granulocytes (4× increase, p < 0.0001), and natural killer cells (2× increase, p = 0.0249) in IC/BPS patients with HL than in unaffected controls (UC). Patients with IC/BPS-HL also had significantly elevated urinary levels of IL-6 (p = 0.0054), TNF-α (p = 0.0064) and IL-13 (p = 0.0304) compared to patients with IC/BPS without HL (IC/BPS-NHL). In contrast, IL-12p70 levels were significantly lower in the patients with HL than in those without these lesions (p = 0.0422). Different cytokines were elevated in the urine of IC/BPS patients with and without HL, indicating that different disease processes are active in IC/BPS patients with and without HL. Elevated levels of CD138+, CD20+, and CD3+ cells in HL are consistent B and T-cell involvement in disease processes within HL.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

AIMS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. METHODS: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. RESULTS: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. CONCLUSIONS: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

Endoscopic Injection of Low Dose Triamcinolone: A Simple, Minimally Invasive, and Effective Therapy for Interstitial Cystitis With Hunner Lesions.

OBJECTIVE: To investigate the efficacy of low dose triamcinolone injection for effectiveness and durability in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner lesions (HL). MATERIALS AND METHODS: Clinical data from patients with HL who underwent endoscopic submucosal injection of triamcinolone were reviewed. Demographics, pre- and postoperative pain and nocturia scores, and long-term clinical outcomes were assessed. Duration of response was estimated by time to repeat procedure. Kaplan-Meier estimator was used to evaluate time to repeat procedure. RESULTS: A total of 36 patients who received injections of triamcinolone between 2011 and 2015 were included. Median age ± standard deviation of patients was 61.5 ± 12.0 years; 28 (77.8%) were female patients and 8 (22.2%) were male patients. Twenty six patients (72.2%) received only 1 set of injections, 8 (22.2%) received 2 sets of injections, and 2 (5.56%) received 3 or more sets of injections. Average time between injections in those receiving more than 1 set of injections was 344.9 days (median: 313.5, range: 77-714). Preprocedural pain scores were 8.3 ± 1.2 (mean ± standard deviation) on Likert pain scale (0-10), and mean postprocedural pain scores at approximately 1 month were 3.8 ± 2.2, P <.001. Mean preprocedural nocturia bother scores was 7.5 ± 2.0 and mean postprocedural nocturia bother scores was 5.1 ± 2.5, P <.001. CONCLUSION: Endoscopic submucosal injection of low dose triamcinolone in patients with IC/BPS with HL is an effective and durable adjunct to existing treatment modalities. This approach is associated with low morbidity and can be performed on an outpatient basis.

Elevated Urine Levels of Macrophage Migration Inhibitory Factor in Inflammatory Bladder Conditions: A Potential Biomarker for a Subgroup of Interstitial Cystitis/Bladder Pain Syndrome Patients.

OBJECTIVE: To investigate whether urinary levels of macrophage migration inhibitory factor (MIF) are elevated in interstitial cystitis/bladder pain syndrome (IC/BPS) patients with Hunner lesions and also whether urine MIF is elevated in other forms of inflammatory cystitis. METHODS: Urine samples were assayed for MIF by enzyme-linked immunosorbent assay. Urine samples from 3 female groups were examined: IC/BPS patients without (N = 55) and with Hunner lesions (N = 43), and non-IC/BPS patients (N = 100; control group; no history of IC/BPS; cancer or recent bacterial cystitis). Urine samples from 3 male groups were examined: patients with bacterial cystitis (N = 50), radiation cystitis (N = 18) and noncystitis patients (N = 119; control group; negative for bacterial cystitis). RESULTS: Urine MIF (mean MIF pg/mL ± standard error of the mean) was increased in female IC/BPS patients with Hunner lesions (2159 ± 435.3) compared with IC/BPS patients without Hunner lesions (460 ± 114.5) or non-IC/BPS patients (414 ± 47.6). Receiver operating curve analyses showed that urine MIF levels discriminated between the 2 IC groups (area under the curve = 72%; confidence interval 61%-82%). Male patients with bacterial and radiation cystitis had elevated urine MIF levels (2839 ± 757.1 and 4404 ± 1548.1, respectively) compared with noncystitis patients (681 ± 75.2). CONCLUSION: Urine MIF is elevated in IC/BPS patients with Hunner lesions and also in patients with other bladder inflammatory and painful conditions. MIF may also serve as a noninvasive biomarker to select IC/BPS patients more accurately for endoscopic evaluation and possible anti-inflammatory treatment.

Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

OBJECTIVES: To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. PATIENTS AND METHODS: The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. RESULTS: An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. CONCLUSIONS: The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability.

Obesity with Comorbid Stress Urinary Incontinence in Women: A Narrative Review to Inform Dietetics Practice.

Stress urinary incontinence (SUI) is a common problem among women; clinical treatment guidelines include weight reduction as a strategy for controlling urinary leakage. The purpose of this review was to gather evidence on the association between obesity and SUI and to ascertain whether there are any special considerations for implementing medical nutrition therapy with community-dwelling, obese, adult females with comorbid SUI. Five key findings emerged: epidemiologic studies consistently report statistically significant associations between obesity and SUI, randomized control trials found that weight loss appears to ameliorate SUI symptoms, the SUI-activity link may affect weight management, there is a potential interplay between SUI and the obesity-sleep connection, and dietary components are associated with the exacerbation of urinary symptoms. The pathogenesis of SUI and obesity-related contributions to urinary leakage is included in the introductory discussion. Lastly, insights on special considerations for implementing nutrition interventions with this population are offered.

Similarities between interstitial cystitis/bladder pain syndrome and vulvodynia: implications for patient management.

Interstitial cystitis/bladder pain syndrome (IC/BPS) and vulvodynia are chronic pain syndromes that appear to be intertwined from the perspectives of embryology, pathology and epidemiology. These associations may account for similar responses to various therapies.

Statistical validation of the shorter-moldwin food sensitivity questionnaire for patients with interstitial cystitis/bladder pain syndrome.

PURPOSE: American Urological Association guidelines suggest dietary changes as first line treatment for interstitial cystitis/bladder pain syndrome. We previously developed a validated survey instrument to determine which foods, beverages and supplements exacerbate the symptoms of this condition. In this study we developed a shortened questionnaire that would provide an easily self-administered food symptom history useful for clinical practice and future research. MATERIALS AND METHODS: Using data from our previously validated food sensitivity questionnaire we remodeled the original lengthy survey to an abbreviated list including the 35 most problematic comestibles. The instrument was reviewed by a panel of experts for face and content validity, and tested for internal consistency, readability and clarity, and test-retest reliability. RESULTS: Of the 124 patients who completed a baseline questionnaire 52 (42%) returned the second instrument 1 week after completing the first instrument. Internal consistency was high (α=0.96). A total of 47 patients (90.4%) indicated that they were food sensitive. Questionnaire test-retest reliability assessed by the Spearman correlation coefficient ranged from moderate (ρ=0.48 for Equal®) to very strong (ρ=0.90 for beer). Discrepancies between the survey instruments in individual comestibles occurred only 1% of the time. CONCLUSIONS: Our short form diet history questionnaire based on a previously validated long form is a reliable, newly validated instrument that will help identify comestibles associated with interstitial cystitis/bladder pain syndrome symptoms. Its brevity makes it simple to administer and useful for dietary management in this population.

Myofascial trigger points of the pelvic floor: associations with urological pain syndromes and treatment strategies including injection therapy.

Myofascial trigger points (MTrP), or muscle "contraction knots," of the pelvic floor may be identified in as many as 85 % of patients suffering from urological, colorectal and gynecological pelvic pain syndromes; and can be responsible for some, if not all, symptoms related to these syndromes. Identification and conservative treatment of MTrPs in these populations has often been associated with impressive clinical improvements. In refractory cases, more "aggressive" therapy with varied trigger point needling techniques, including dry needling, anesthetic injections, or onabotulinumtoxinA injections, may be used, in combination with conservative therapies.

Effects of foods and beverages on the symptoms of chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To better elucidate the prevalence of perceived food sensitivity and characterize the sensitivity pattern in patients with clinically diagnosed chronic prostatitis/chronic pelvic pain syndrome. METHODS: A total of 286 men meeting the National Institutes of Health criteria for chronic prostatitis were mailed a validated questionnaire designed to detect the effect of foods, beverages, and/or supplements on pelvic pain symptoms. The questionnaire assessed the effect of 176 individual comestibles on each patient's symptoms. The responses were numerically scored on a scale of -2 to +2, and the mean values were generated for each comestible. In addition, the participants were asked to complete the O'Leary-Sant Symptom and Problem Index and Chronic Prostatitis Symptom Index questionnaires. RESULTS: Of the 286 surveys, 95 were returned, yielding a response rate of 33.2%. Of those subjects who responded, 47.4% reported that the consumption of certain comestibles aggravated their symptoms, with the most aggravating being spicy foods, coffee, hot peppers, alcoholic beverages, tea, and chili. In contrast, the comestibles that alleviated the symptoms the most included docusate, pysllium, water, herbal teas, and polycarbophil. CONCLUSION: Many patients with chronic prostatitis/chronic pelvic pain syndrome have demonstrable food, beverage, and dietary supplement sensitivities. Dietary changes should be considered in the treatment of these patients.

Fulguration for Hunner ulcers: long-term clinical outcomes.

PURPOSE: Cystoscopic fulguration of Hunner ulcers in patients with interstitial cystitis/bladder pain syndrome is a recommended therapy because it has the potential to rapidly ameliorate symptoms. We reviewed our experience with Hunner ulcer fulguration. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with interstitial cystitis/bladder pain syndrome treated with Hunner ulcer fulguration who were seen at our pelvic pain referral center between 1993 and 2011. Patient demographics, clinical characteristics, intraoperative findings and long-term clinical outcomes were assessed. The Kaplan-Meier product limit method was used to evaluate time to the first repeat procedure. Potential risk factors associated with repeat procedures were examined using the log rank test. RESULTS: A total of 106 procedures were performed in 59 patients. The mean history of illness before first fulguration was 5 years and overall median followup was 44.8 months (IQR 52.2), as calculated from the time of the first fulguration. There were no significant associations between time to the first repeat procedure and any demographic criteria analyzed, patient reported interstitial cystitis/bladder pain syndrome associated conditions or the number of Hunner ulcers fulgurated at the initial session. A total of 27 patients (45.8%) required repeat fulguration. Time to event analysis demonstrated that 12 months after the initial fulguration 13.1% of patients required repeat treatment. This rate increased to 57.2% at 48 months, when it plateaued. CONCLUSIONS: Fulguration of Hunner ulcers can be an effective treatment for patients with interstitial cystitis/bladder pain syndrome and focal Hunner ulcers involving less than 25% of the bladder who have symptoms refractory to other therapies. However, a significant subset requires repeat treatment and some patients may even go on to require cystectomy.

The impact of neuropathic pain in the chronic pelvic pain population.

PURPOSE: Patients with chronic pelvic pain disorders often present with neuropathic features. We examined a cohort of patients with a primary complaint of chronic pelvic pain for the presence of neuropathic pain symptoms. MATERIALS AND METHODS: Patients with chronic pelvic pain disorders from 2 tertiary referral centers were prospectively evaluated. The validated S-LANSS (Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs) survey was used to examine pain symptoms of neuropathic origin. Patients completed SF-12v2™ to assess mental/physical health domains. The 2-tailed t test and chi-square analysis were used to compare physical and mental component summaries in patients with vs without neuropathic symptoms. RESULTS: A total of 142 patients mean age of 45 years were included in analysis. Of the patients 72.5% with chronic pelvic pain carried more than 1 primary diagnosis. The S-LANSS survey identified symptoms suggestive of neuropathic pain in 44 patients (31%). A greater proportion of patients with a neuropathic component had altered sensation in the affected area (86.4% vs 24.5%). Patients with neuropathic pain scored 4.28 and 5.45 points lower on the physical and mental component summaries (p = 0.053 and 0.008, respectively). CONCLUSIONS: A large proportion of patients with chronic pelvic pain present with neuropathic features and report decreased quality of life compared with the general population. Those with neuropathic symptoms have significantly lower quality of life than those without such symptoms. Clinicians can identify patients to use targeted therapies and use a multidisciplinary approach to care.

Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions.

What's known on the subject? and What does the study add? Nearly 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of dietary comestibles. Current questionnaire-based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. At present we recommend employing a controlled method to determine dietary sensitivities, such as an elimination diet, in order to identify sensitivities while at the same time maintain optimal nutritional intake. We review current literature with regard to diet's effect upon IC/BPS and common comorbidities (irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, neuropathic pain, vulvodynia, and headache) with a focus upon questionnaire-based investigations. We discuss the pathologic mechanisms that may link diet and IC/BPS related-pain, concentrating upon specific comestibles such as acidic foods, foods high in potassium, caffeine, and alcohol. Up to 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of comestibles. Pathological mechanisms suggested to be responsible for the relationship between dietary intake and symptom exacerbation include peripheral and/or central neural upregulation, bladder epithelial dysfunction, and organ 'cross-talk', amongst others. Current questionnaire-based data suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. Specific comestible sensitivities varied between patients and may have been influenced by comorbid conditions. This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management.

Symptom profile variability of interstitial cystitis/painful bladder syndrome by age.

UNLABELLED: Study Type--Diagnostic (symptom prevalence). Level of Evidence 2b. What's known on the subject? And what does the study add? Symptom variability is profound in the population of patients diagnosed with interstitial cystitis and painful bladder syndrome because these diagnoses represent a very heterogeneous patient population. Recently, younger patients are being diagnosed with these pain syndromes, without any specific investigation into the symptoms they experience. We identified that patients diagnosed with interstitial cystitis and painful bladder syndrome have variable clinical symptom profiles depending on the age at the time of their diagnosis. Dyspareunia, external genitalia pain, urgency, frequency and dysuria were more common in younger patients whereas nocturia, urinary incontinence and the presence of Hunner's ulcers were more common in older patients. Better defining symptom profiles for patients at the time of evaluation may potentially aid in more accurate and expedited diagnosis of these conditions, particularly in the youngest patient population which is being recognized more commonly in recent times. OBJECTIVE: • To investigate the clinical profile differences among patients with interstitial cystitis/painful bladder syndrome (IC/PBS) based upon age at the time of diagnosis from childhood into the geriatric age group. METHODS: • An analysis of 268 patients with IC/PBS seen between 1990 and 2008 was performed. • Three age cohorts were analysed: <30 years, ≥30 years but <60 years, and ≥60 years of age at time of diagnosis. • Patient demographics, disease characteristics and IC/PBS-associated symptoms were compared across the three groups. RESULTS: • Of the 268 patients, 60 were <30 years of age at the time of IC diagnosis (median 22, range 11-29), 105 were ≥30 but <60 years (median 48, range 30-59) and 103 patients were ≥60 years of age (median 69, range 60-88). • Of the patients in the youngest, middle and oldest age cohorts: 12.0, 42.0 and 39.8% had Hunner's ulcers, respectively (P<0.001). • Dyspareunia and external genitalia pain were more common in the youngest age cohort, P<0.001 and P=0.001, respectively. • Urinary urgency (P=0.033), frequency (P=0.006) and dysuria (P<0.001) were also more common in patients diagnosed before 30 years of age. • The reported rate of nocturia and urinary incontinence increased with age, P=0.002 and P<0.001, respectively. CONCLUSIONS: • Patients with IC/PBS analysed across a wide spectrum of ages at time of diagnosis portrayed a unique symptom profile pattern. • Patients diagnosed at the youngest ages experienced significantly more urinary urgency, frequency, dysuria, dyspareunia and pain in their external genitalia. • Older patients had higher rates of nocturia, urinary incontinence and Hunner's ulcer disease.

Effect of comestibles on symptoms of interstitial cystitis.

PURPOSE: Anecdotal evidence suggests that patients with painful bladder syndrome/interstitial cystitis report symptom exacerbation after consuming particular foods, beverages and/or supplements. We determined the prevalence of the effect of comestibles on painful bladder syndrome/interstitial cystitis symptoms and identified particular comestible items more likely to affect such symptoms. MATERIALS AND METHODS: A validated questionnaire designed to detect whether food, beverages and/or supplements have an effect on bladder symptoms was administered to 104 patients meeting National Institute for Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis. In addition to answering general questions about the effect of comestibles on painful bladder syndrome/interstitial cystitis symptoms, subjects were asked to indicate whether each of 175 individual items worsened, improved or had no effect on symptoms. Each response was numerically scored on a scale of -2 to 2 and mean values were generated for each comestible item. RESULTS: Of the surveyed patients with painful bladder syndrome/interstitial cystitis 90.2% indicated that the consumption of certain foods or beverages caused symptom exacerbation. There was no correlation between allergies and the effect of comestibles on symptoms. Patients who reported that specific foods worsened symptoms tended to have higher O'Leary-Sant interstitial cystitis symptom index and problem index, and/or pelvic pain and urgency/frequency patient symptom scale scores. A total of 35 comestible items had a mean score of lower than -1.0, including caffeinated, carbonated and alcoholic beverages, certain fruits and juices, artificial sweeteners and spicy foods. CONCLUSIONS: There is a large cohort of patients with painful bladder syndrome/interstitial cystitis in whom symptoms are exacerbated by the ingestion of specific comestibles. The most frequently reported and most bothersome comestibles were coffee, tea, soda, alcoholic beverages, citrus fruits and juices, artificial sweeteners and hot pepper.

Bladder defense molecules, urothelial differentiation, urinary biomarkers, and interstitial cystitis.

It has long been recognized that interstitial cystitis (IC) is a disease of the urothelium. In this article, we review the results of published studies and present new data concerning the precise role of the bladder epithelium in IC. We discuss bladder defenses against both the penetration of urinary solutes and bacterial adherence, and we present new information about the proteoglycans that are present on the normal bladder. Previously published results and new data presented here support the conclusion that IC involves an aberrant differentiation program in the bladder urothelium that leads to altered synthesis of several proteoglycans, cell adhesion and tight junction proteins, and bacterial defense molecules such as GP51. These findings lend support to the rationale for glycosaminoglycan replacement therapy for the treatment of patients with IC.

Chronic prostatitis/chronic pelvic pain syndrome and male interstitial cystitis: enigmas and opportunities.

Recently, it has been recognized that interstitial cystitis (IC) in males is a more common clinical entity than was previously thought. Further, increasing evidence suggests clinical and pathogenetic similarities between male IC and chronic nonbacterial prostatitis (CP)/chronic pelvic pain syndrome. In this article, we highlight the similarities and differences between male IC and CP and review the presentation, diagnosis, and treatment of IC in men, with particular attention to those who have received an initial diagnosis of CP.