New literature on interstitial cystitis and relevant subjects
click on the title to jump to the abstract - latest update 27 December 2012
RANDOMIZED MULTICENTER FEASIBILITY TRIAL OF MYOFASCIAL PHYSICAL THERAPY FOR THE TREATMENT OF UROLOGICAL CHRONIC PELVIC PAIN SYNDROMES. Fitzgerald MP, Anderson RU, Potts J, Payne CK, Peters KM, Clemens JQ, Kotarinos R, Fraser L, Cosby A, Fortman C, Neville C, Badillo S, Odabachian L, Sanfield A, O'Dougherty B, Halle-Podell R, Cen L, Chuai S, Landis JR, Mickelberg K, Barrell T, Kusek JW, Nyberg LM; Urological Pelvic Pain Collaborative Research Network.J Urol. 2013 Jan;189(1 Suppl):S75-85. doi: 10.1016/j.juro.2012.11.018. PMID: 23234638
The aim of this study was to determine the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. 48 subjects (23 men and 24 women) with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome were recruited at 6 clinical centers. Of the patients 24 were randomized to global therapeutic massage, 23 to myofascial physical therapy and 44 completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group. The authors considered it feasible to conduct a full-scale trial of physical therapy methods and felt that the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.
pain in IC/BPS subtypes
PAIN IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME: DO CHARACTERISTICS DIFFER IN ULCERATIVE AND NON-ULCERATIVE SUBTYPES? Killinger KA, Boura JA, Peters KM. Int Urogynecol J. 2012 Dec 4. [Epub ahead of print] PMID: 23208005
Killinger et al hypothesized that pain characteristics in women grouped by IC/BPS subtype would differ. A survey was mailed to 749 women to assess IC/BPS pain and other characteristics. Of the 214 women that returned a survey (36 ulcerative and 178 non-ulcerative IC/BPS), similar proportions in each group reported that certain foods, exercise, and/or stress triggered symptoms. Fewer ulcerative patients reported pain with vaginal penetration than non-ulcerative. On the BPI, the ulcerative and non-ulcerative groups reported similar numbers of painful areas, and lower abdominal/pelvic pain was reported most, followed by lower back pain. Even though ICSI-PI, MPQ-SF, and BPI scores/responses did not differ, on the MPQ-SF the three words most frequently used by ulcerative patients to describe their pain were sharp, stabbing, and hot burning, and in non-ulcerative were aching, cramping, and tender. These measures did not reveal any significant differences in pain between subtypes. More research is needed in larger samples to determine whether differences exist.
ILLICIT KETAMINE AND ITS BLADDER CONSEQUENCES: IS IT IRREVERSIBLE? Jalil R, Gupta S. BMJ Case Rep. 2012 2012 Oct 30;2012. pii: bcr2012007244. doi: 10.1136/bcr-2012-007244
Ketamine bladder is a new clinical entity that may lead to irreversible damage to the urinary system. We report the severe lower urinary tract symptoms of four young patients referred to our urology unit who were found to have ulcerative cystitis secondary to ketamine abuse. The pathophysiology remains unclear and the treatment is symptomatic.
KETAMINE CYSTITIS: AN EMERGING DIAGNOSTIC AND THERAPEUTIC CHALLENGE. Gray T, Dass M. Br J Hosp Med (Lond). 2012 Oct;73(10):576-9. PMID: 23124288
Ketamine abuse is increasingly common in the UK. Ketamine-induced cystitis can cause serious damage to the urinary tract. This emerging problem presents a new diagnostic challenge and is very likely to increase in incidence over the coming years.
PROGNOSTIC FACTORS FOR RECENT-ONSET INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME. Warren JW, Clauw DJ, Langenberg P. BJU Int. 2012 Aug 9. doi: 10.1111/j.1464-410X.2012.11422.x. [Epub ahead of print]. PMID: 22882525
In a prospective study of 304 incident female IC/PBS cases followed for a median of 33 months after onset, women with baseline chronic fatigue syndrome had a worse prognosis for IC/PBS. The authors concluded that at a median of nearly 3 years after onset, baseline mild IC/PBS was directly associated with a milder disease severity. Baseline co-morbid CFS was associated with more severe disease. Whether CFS was uniquely associated or represented several co-morbid non-bladder syndromes (NBSs) could not be determined.
QoL in IC/BPS and comorbidities
HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME AND FREQUENTLY ASSOCIATED COMORBIDITIES. Suskind AM, Berry SH, Suttorp MJ, Elliott MN, Hays RD, Ewing BA, Clemens JQ. Qual Life Res. 2012 Oct 7. [Epub ahead of print] PMID: 23054497
The purpose of this study was to estimate the association of chronic non-urologic conditions [i.e., fibromyalgia (FM), chronic fatigue syndrome (CFS), and irritable bowel syndrome (IBS)] with health-related quality of life (HRQOL) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). It was concluded that in patients with IC/BPS, the presence of FM, CFS, and IBS has a significant association with HRQOL, equivalent in impact to the bladder symptoms themselves. These results emphasize the importance of a multidisciplinary approach to treating patients with IC/BPS and other conditions.
COMORBIDITIES OF INTERSTITIAL CYSTITIS Chelimsky G, Heller E, Buffington CA, Rackley R, Zhang D, Chelimsky T. Front Neurosci. 2012;6:114. Epub 2012 Aug 10. PMID: 22907988. Free full text This study demonstrates widespread co- morbidities in patients with interstitial cystitis, both physician and questionnaire diagnosed, with very similar findings in the two groups. Known co-morbid disorders were confirmed, including migraine headache, IBS, and widespread pain. New co-morbidities emerged, including dyspepsia-like symptoms and orthostatic intolerance. The multiple involvement of organ systems far from the bladder supports the theory that IC/BPS is not a primary bladder disorder, but rather that the bladder is one more organ system involved in a systemic, possibly neurologic disorder.
A CASE-CONTROL STUDY ON THE ASSOCIATION BETWEEN RHEUMATOID ARTHRITIS AND BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS. Keller JJ, Liu SP, Lin HC. Neurourol Urodyn. 2012 Nov 5. doi: 10.1002/nau.22348. [Epub ahead of print]. PMID: 23129416
This study from Taiwan included 9,269 cases with BPS/IC and 46,345 randomly selected controls. RA was found among 202 (2.2%) cases and 504 (1.12%) controls. Conditional logistic regression analysis suggested that when compared with controls, the odds ratio for prior RA among cases was 1.66 after adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use disorder, and alcohol abuse. Additionally, BPS/IC was consistently and significantly associated with a previous diagnosis of RA regardless of prescription drug use. It was concluded that there is indeed an association between RA and BPS/IC after adjusting for socio-demographic characteristics and medical co-morbidities.
COMORBIDITIES OF BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS: A POPULATION-BASED STUDY. Keller JJ, Chen YK, Lin HC. BJU Int. 2012 Sep 28. doi: 10.1111/j.1464-410X.2012.11539.x. [Epub ahead of print] PMID: 23020942
This study from Taiwan explored the comorbid medical conditions of patients with BPS/IC in Taiwan using a cross-sectional study design and a population-based administrative database. With the exception of metastatic cancer, the subjects with BPS/IC had a significantly higher prevalence of all the medical comorbidities analysed than subjects without BPS/IC. When compared with subjects without BPS/IC, subjects with BPS/IC had particularly higher odds of comorbid neurological diseases, rheumatological diseases and mental illnesses. The authors concluded that their results indicated that subjects with BPS/IC had an increased prevalence of multiple comorbidities.
FULGURATION FOR HUNNER ULCERS: LONG-TERM CLINICAL OUTCOMES. Hillelsohn JH, Rais-Bahrami S, Friedlander JI, Okhunov Z, Kashan M, Rosen L, Moldwin RM. J Urol. 2012 Dec;188(6):2238-41. doi: 10.1016/j.juro.2012.08.013. Epub 2012 Oct 22. PMID: 23083651
Hillelsohn and colleagues concluded that 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.
IC and OAB
INTERSTITIAL CYSTITIS AND THE OVERLAP WITH OVERACTIVE BLADDER. Elliott CS, Payne CK. Curr Urol Rep. 2012 Oct;13(5):319-26. PMID: 22965225
The overlap between interstitial cystitis-painful bladder syndrome and overactive bladder can present a diagnostic challenge to the treating practitioner. Both can present with similar patient symptoms. Further compounding this dilemma is the fact that no gold standard test exists to differentiate one from the other. This review highlights their similarities and distinguishing features.
INTRAVESICAL HYALURONIC ACID FOR INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME: A COMPARATIVE RANDOMIZED ASSESSMENT OF DIFFERENT REGIMENS. Lai MC, Kuo YC, Kuo HC. Int J Urol. 2012 Aug 26. doi: 10.1111/j.1442-2042.2012.03135.x. [Epub ahead of print]. PMID: 22925498
This study compared the clinical effectiveness of different regimens of intravesical hyaluronic acid instillation for patients with interstitial cystitis/painful bladder syndrome. A total of 60 patients (age 16-77 years) diagnosed with interstitial cystitis/painful bladder syndrome were enrolled in this prospective, randomized study. A total of 30 patients were assigned to receive four weekly intravesical instillations of 40mg of hyaluronic acid followed by five monthly instillations (hyaluronic acid-9 group). Another 30 patients received 12 intravesical instillations of 40mg hyaluronic acid every 2 weeks (hyaluronic acid-12 group). The measured variables did not differ between the two groups over the course of the study. It was therefore concluded that no significant difference was noted in the therapeutic effect between two hyaluronic acid instillation regimens for treatment of interstitial cystitis/painful bladder syndrome patients. Both groups showed significant improvement in symptom scores and Quality of Life Index.
NERVOUS NETWORK FOR LOWER URINARY TRACT FUNCTION Birder LA. Int J Urol. 2012 Oct 23. doi: 10.1111/j.1442-2042.2012.03210.x. [Epub ahead of print]. PMID: 23088378. Free access
This review discusses some of the components involved in control of lower urinary tract function, with an emphasis on the sensor and transducer roles of the urothelium.
CLINICAL CHARACTERISTICS DIFFER CONSIDERABLY BETWEEN PHENOTYPES OF BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS. Logadottir Y, Fall M, Kåbjörn-Gustafsson C, Peeker R. Scand J Urol Nephrol. 2012 Oct;46(5):365-70. doi: 10.3109/00365599.2012.689008. Epub 2012 May 21. PMID: 22607036
Logadottir et al note that BPS/IC includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated European Society for the Study of Interstitial Cystitis (ESSIC) type 3C, the non-Hunner type of BPS/IC appears to be different with regard to demographic, endoscopic and histological findings, as well as the response to all forms of treatment. The objective of this study was to determine whether there are additional dissimilarities in clinical presentation between the main phenotypes of BPS/IC. In total, 393 BPS/IC patients (210 type 3C and 183 non-Hunner), diagnosed according to NIDDK and ESSIC criteria, were studied by surveying the clinical records including micturition diaries. The authors concluded that the findings in the present series, together with previously published reports by this group and by others, confirm the striking differences between the main forms of BPS/IC and underline the indispensability of adequate subtyping in clinical studies.
ENHANCED UROTHELIAL EXPRESSION OF HUMAN CHORIONIC GONADOTROPIN BETA (HCGΒ) IN BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS (BPS/IC). Schwalenberg T, Stolzenburg JU, Thi PH, Mallock T, Hartenstein S, Alexander H, Zimmermann G, Hohenfellner R, Denzinger S, Burger M, Horn LC, Neuhaus J. World J Urol. 2012 Jun;30(3):411-7. Epub 2011 Aug 30. PMID: 21877171
The aims of this study were to examine the expression of human chorionic gonadotropin (hCG )and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls. They found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients. They concluded that the constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. They show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Their findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. They concluded that hCG could have relevance for treatment in the future.
MAPPING OF PAIN PHENOTYPES IN FEMALE PATIENTS WITH BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS AND CONTROLS. Tripp DA, Nickel JC, Wong J, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J. Eur Urol. 2012 Dec;62(6):1188-94. doi: 10.1016/j.eururo.2012.05.023. Epub 2012 May 18. PMID: 22633363
Many BPS/IC patients report multiple pain locations outside the pelvis. This study compared and contrasted pain in BPS/IC patients and controls using a whole-body diagram (visible body areas) and examined the association between patient adjustment factors and greater number of body pain areas (pain phenotypes). Patients reported numerous systemic pain symptoms outside the areas associated with the bladder/pelvic region, and increased numbers of body pain sites were associated with poorer patient outcomes (ie, pain severity, depression). This study illustrates the significant negative impact of pain on patient adjustment in BPS/IC.
A MOUSE MODEL FOR INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME BASED ON APF INHIBITION OF BLADDER EPITHELIAL REPAIR: A PILOT STUDY. Keay S, Leitzell S, Ochrzcin A, Clements G, Zhan M, Johnson D. BMC Urol. 2012 Jun 8;12(1):17. [Epub ahead of print]. PMID: 22682521. Free text
Keay et al determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice. On the basis of their results, they believe that this model demonstrates in vivo effects of as-APF which abrogates bladder epithelial repair and expression of UPIII and ZO-1 in CBA/J mice following transurethral acetic acid infusion. As bladder epithelial thinning, decreased UPIII expression, and decreased ZO-1 expression are histopathologic features of IC/PBS patient biopsies, this model may be useful for studying the pathophysiology of IC/PBS and the effect of potential therapies.
disability in IC/BPS
DISABILITY IN WOMEN SUFFERING FROM INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME. Katz L, Tripp DA, Nickel JC, Mayer R, Reimann M, van Ophoven A. BJU Int. 2012 May 11. doi: 10.1111/j.1464-410X.2012.11238.x. [Epub ahead of print]. PMID: 22578191
The findings of this study suggest that psychosocial factors are significant in mediating the relationship between impairments and patient disability, with negative affect (i.e. depression, anxiety) and pain catastrophizing acting as significant mediators. Questionnaires completed by 196 women with IC/BPS provided data for the present study. It was concluded that disability in patients suffering from IC/BPS is partially explained by the impact of negative effect and catastrophizing. As a result of the refractory nature of IC/BPS, patient management within a biopsychosocial framework represents an essential area of investigation. Decreases in negative effect and catastrophizing will probably lead to improvements in pain-related disability.
INTRAVESICAL HYALURONIC ACID AND ALKALINIZED LIDOCAINE FOR THE TREATMENT OF SEVERE PAINFUL BLADDER SYNDROME/INTERSTITIAL CYSTITIS. Lv YS, Zhou HL, Mao HP, Gao R, Wang YD, Xue XY. Int Urogynecol J. 2012 Dec;23(12):1715-20. doi: 10.1007/s00192-012-1802-3. Epub 2012 May 11. PMID: 22576327
This study from Fujian, People's Republic of China, looked at the use of intravesical instillation of hyaluronic acid (HA) to restore the integrity of the glycosaminoglycan(GAG) layer in patients with painful bladder syndrome/interstitial cystitis (PBS/IC), and how the benefit may be improved with the addition of alkalinized lidocaine (AL). The authors concluded that intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study.
INTRAVESICAL HYALURONIC ACID AND CHONDROITIN SULPHATE FOR BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS: LONG-TERM TREATMENT RESULTS. Cervigni M, Natale F, Nasta L, Mako A. Int Urogynecol J. 2012 Sep;23(9):1187-92. doi: 10.1007/s00192-012-1742-y. Epub 2012 May 9. PMID: 22569687
Reconstruction of the glycosaminoglycan (GAG) layer is believed to play a role in the successful treatment of bladder pain syndrome/interstitial cystitis (BPS/IC). Intravesical instillations of hyaluronic acid (HA) and chondroitin sulphate (CS) have given results in the short term. Cervigni and colleagues found that intravesical instillations of HA and CS produced a sustained improvement of symptoms, up to 3 years, in patients with BPS/IC refractory to previous treatments. Further confirmation would be expected from larger controlled trials.
URINARY CHEMOKINES AS NONINVASIVE PREDICTORS OF ULCERATIVE INTERSTITIAL CYSTITIS. Tyagi P, Killinger K, Tyagi V, Nirmal J, Chancellor M, Peters KM. J Urol. 2012 Jun;187(6):2243-8. Epub 2012 Apr 13. PMID: 22503040
Tyagi et al tested the hypothesis that select chemokines are increased in the urine of patients with ulcerative and nonulcerative interstitial cystitis/painful bladder syndrome, concluding that differential expression of chemokines in ulcerative and nonulcerative subtypes of interstitial cystitis/painful bladder syndrome suggests differences in paracrine signalling between the 2 entities.
Comment in: Identifying biomarkers for interstitial cystitis/bladder pain syndrome. [J Urol. 2012]
Identifying biomarkers for interstitial cystitis/bladder pain syndrome. Erickson DR. J Urol. 2012 Jun; 187(6):1958-9. Epub 2012 Apr 11.
RANDOMIZED MULTICENTER CLINICAL TRIAL OF MYOFASCIAL PHYSICAL THERAPY IN WOMEN WITH INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME AND PELVIC FLOOR TENDERNESS. FitzGerald MP, Payne CK, Lukacz ES, Yang CC, Peters KM, Chai TC, Nickel JC, Hanno PM, Kreder KJ, Burks DA, Mayer R, Kotarinos R, Fortman C, Allen TM, Fraser L, Mason-Cover M, Furey C, Odabachian L, Sanfield A, Chu J, Huestis K, Tata GE, Dugan N, Sheth H, Bewyer K, Anaeme A, Newton K, Featherstone W, Halle-Podell R, Cen L, Landis JR, Propert KJ, Foster HE jr, Kusek JW, Nyberg LM; Interstitial Cystitis Collaborative Research Network. Collaborators (48): Miller J, Muller CH, Kalhoff J, Bassuk J, Downing S, Bale RF Jr, Shinghal R, Anderson R, Clay D, Ramakrishnan A, Nager C, Chenoweth M, Anton E, Wolfert C, Lampkins L, Keay S, Dinh R, Sangrampurkar R, Morales A, Emerson L, Carr L, Downey J, Clark-Pereira J, Robb S, Brubaker L, Rindels J, Bucher G, Newman DK, Salazar S, Milado J, Moy L, O'Donnell M, Lutgendorf S, Eno M, O'Berry K, Rivers K, Romero S, Peabody M, Messing E, Smith EB, Rust K, Reeder J, Mickelberg K, Barrell T, Chuai S, Mullins C, Harris M, Ratner V. J Urol. 2012 Jun;187(6):2113-8. Epub 2012 Apr 12. PMID: 22503015
This team determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic IC/PBS. They found that a significantly higher proportion of women with IC/PBS responded to treatment with myofascial physical therapy than to global therapeutic massage.
ZO-1 in OAB and IC/BPS
DIFFERENCES IN MAST CELL INFILTRATION, E-CADHERIN, AND ZONULA OCCLUDENS-1 EXPRESSION BETWEEN PATIENTS WITH OVERACTIVE BLADDER AND INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME. Liu HT, Shie JH, Chen SH, Wang YS, Kuo HC. Urology. 2012 Jul;80(1):225.e13-8. Epub 2012 Apr 21. PMID: 22521193
Liu et al investigated the difference of infiltration of mast cells and the distribution of protein involved in the urothelial barrier function between patients with overactive bladder syndrome (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Bladder wall biopsies were performed in 27 patients with OAB, 18 patients with IC/BPS, and 19 controls. The numbers of mast cells in the urothelium and suburothelium areas were low in the control group. A highly significant increase in mast cell infiltration was observed in OAB and IC/BPS specimens. ZO-1 expression was significantly decreased in IC/PBS compared with OAB and control bladder samples. The E-cadherin expression was also significantly decreased in IC/BPS bladder samples compared with the controls. No significant difference was found in E-cadherin or ZO-1 levels between the OAB and control bladders. Mast cell infiltration was found in both OAB and IC/BPS bladder wall, but E-cadherin and ZO-1 expression was only decreased in IC/BPS, suggesting that the urothelial barrier function was not affected in the OAB bladder.
reflux esophagitis and BPS/IC
REFLUX ESOPHAGITIS INCREASED THE RISK OF BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS: A 3-YEAR FOLLOW-UP STUDY. Kang JH, Keller JJ, Chen YK, Lin HC. Neurourol Urodyn. 2012 Jun 5. doi: 10.1002/nau.22270. [Epub ahead of print]. PMID: 22674619
This study from Taiwan explored the association between BPS/IC and reflux esophagitis (RE). The incidence of BPS/IC following a diagnosis of RE was 4.3% during the follow-up period for all subjects. The authors found that patients with RE were at a higher risk than with comparison patients for having been subsequently diagnosed with BPS/IC during longitudinal follow-up. They suggest that their results can provide a basis to explore non-esophageal disease in RE patients, but emphasise that further studies are advised to confirm their findings and elucidate the pathomechanism underpinning the associations detected in this study.
OAB and fibromyalgia
THE ASSOCIATION BETWEEN OVERACTIVE BLADDER AND FIBROMYALGIA SYNDROME: A COMMUNITY SURVEY. Chung JH, Kim SA, Choi BY, Lee HS, Lee SW, Kim YT, Lee TY, Moon HS. Neurourol Urodyn.2013 Jan;32(1):66–69. PMID: 22674758
This study from Korea focuses on the association of overactive bladder (OAB) and FMS in adults aged 40 and over. A survey of adults aged 40s and over was conducted in the Guri and Yangpyeong areas of South Korea. The association between FMS and severity of OAB was statistically significant. The authors concluded that OAB is associated with FMS and that FMS increases with severity of OAB. They suggest that a large scale study should be performed by medical specialists (urologists, rheumatologists) to further evaluate the patients and identify the basis of the association between the two diseases.
HOW DOES THE UROTHELIUM AFFECT BLADDER FUNCTION IN HEALTH AND DISEASE?: ICI-RS 2011. Birder L, Ruggieri M, Takeda M, van Koeveringe G, Veltkamp S, Korstanje C, Parsons B, Fry C. Neurourol Urodyn. 2012 Mar;31(3):293-9. doi: 10.1002/nau.22195. Epub 2012 Jan 24. PMID: 22275289
This review considers the nature of the stresses that the urothelium can transduce; the transmitters that mediate the transduction process; and how lower urinary pathologies, including overactive bladder syndrome, painful bladder syndrome and bacterial infections, are associated with alterations to this sensory system. The authors conclude by saying: “The lower urinary tract is ideally suited for minimally invasive intravesical treatments. Thus, continued research efforts are needed not only to improve our understanding of the pathophysiological mechanisms that underlie bladder dysfunction, but also to improve our knowledge of the chemical and physical properties of the bladder wall and the processes that regulate drug transport across it.”
DIET AND ITS ROLE IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME (IC/BPS) AND COMORBID CONDITIONS. Friedlander JI, Shorter B, Moldwin RM. BJU Int. 2012 Jun;109(11):1584-91. doi: 10.1111/j.1464-410X.2011.10860.x. Epub 2012 Jan 11. PMID: 22233286
Friedlander and colleagues from the US note that 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 they 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. In this article, they 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. They 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.
LONG-TERM EXPERIENCE WITH SURGICAL TREATMENT OF SELECTED PATIENTS WITH BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS. Andersen AV, Granlund P, Schultz A, Talseth T, Hedlund H, Frich L. Scand J Urol Nephrol. 2012 Aug;46(4):284-9. doi: 10.3109/00365599.2012.669789. Epub 2012 Mar 27. PMID: 22452583
This report from Oslo, Norway presents a single-institution experience with major surgery in 41 patients with disabling BPS/IC where conservative treatment had failed. Surgical approach was determined on a case-by-case basis. Postoperative pain and satisfaction were assessed by a questionnaire. There was no difference in reported pain between cystectomized and non-cystectomized patients. When comparing patients who reported pain at follow-up with those who did not report pain, preoperative length of symptoms was significantly increased, with 12.1 compared to 5.4 years. The authors concluded that major surgery is associated with good symptom relief in strictly selected patients with disabling BPS/IC, where conservative treatment has failed. Extended preoperative duration of symptoms may be a predictor for persisting pain after major surgery for BPS/IC.
neurol cross-talk and afferent sensitization
TRANSIENT RECEPTOR POTENTIAL A1 RECEPTOR-MEDIATED NEURAL CROSS-TALK AND AFFERENT SENSITIZATION INDUCED BY OXIDATIVE STRESS: IMPLICATION FOR THE PATHOGENESIS OF INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME. Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N. Int J Urol. 2012 May;19(5):429-36. doi: 10.1111/j.1442-2042.2012.02966.x. Epub 2012 Feb 21. PMID: 22353309
In this review from Pittsburgh and Tokyo, Furuta and colleagues highlight evidence supporting neural cross-talk in the dorsal root ganglia, spinal cord and brain levels, which might play a role in the development of chronic pain disorders through central sensitization. In addition, they focus on transient receptor potential V1 and transient receptor potential A1 as the receptor targets for chronic pain conditions, because transient receptor potential V1 and transient receptor potential A1 act as a nocisensor to mediate not only an afferent signal to the dorsal horn of the spinal cord, but also an efferent signal in the periphery through secretion of inflammatory agents, such as substance P and calcitonin gene-related peptide in nociceptive sensory neurons.
bladder and bowel
DO THE URINARY BLADDER AND LARGE BOWEL INTERACT, IN SICKNESS OR IN HEALTH?: ICI-RS 2011. Malykhina AP, Wyndaele JJ, Andersson KE, De Wachter S, Dmochowski RR. Neurourol Urodyn. 2012 Mar;31(3):352-8. doi: 10.1002/nau.21228. Epub 2012 Feb 29. PMID: 22378593
This review summarizes clinical data on colon-bladder cross-reflexes in healthy individuals, as well as in patients with co-morbid disorders. It also discusses currently used animal models, experimental approaches, suggested mechanisms of colon-bladder cross-talk and provides an overview of the potential pharmacological targets to develop treatment options for patients with co-morbid disorders. The presented work resulted from the discussion of colon/bladder interactions during "Think Tank 9" presentations at the International Consultation on Incontinence Research Society meeting held in Bristol, UK, 2011.
CONTEMPORARY MANAGEMENT OF THE PAINFUL BLADDER: A SYSTEMATIC REVIEW. Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ. Eur Urol. 2012 Jan;61(1):29-53. Epub 2011 Sep 9. PMID: 21920661 Free access
A review of data from a wide range of current therapeutic approaches to PBS/IC, quantifying the effect size from randomised controlled trials (RCTs), and determining the efficacy of treatments for PBS/IC. They concluded that limited evidence exists for the few treatments for PBS/IC. The lack of definitive conclusions is due to the great heterogeneity in methods used, assessment of symptoms, duration of treatment, and follow-up in both RCTs and nRCTs.
THE BLADDER PAIN/INTERSTITIAL CYSTITIS SYMPTOM SCORE: DEVELOPMENT, VALIDATION, AND IDENTIFICATION OF A CUT SCORE. Humphrey L, Arbuckle R, Moldwin R, Nordling J, van de Merwe JP, Meunier J, Crook T, Abraham L. Eur Urol. 2012 Feb;61(2):271-9. Epub 2011 Oct 18. PMID: 22050826
This Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) was developed in response to a felt need for a patient-reported symptom-based instrument for clinical trial eligibility of bladder pain/interstitial cystitis patients. It was concluded that the BPIC-SS is a reliable, valid, and appropriate questionnaire to select bladder pain/interstitial cystitis patients for clinical trials.
hyaluronic acid and chondroitin sulphate
THE ROLE OF SODIUM HYALURONATE AND SODIUM CHONDROITIN SULPHATE IN THE MANAGEMENT OF BLADDER DISEASE. Damiano R, Cicione A. Ther Adv Urol. 2011 Oct;3(5):223-32. PMID: 22046200 Free Access
The aim of this article was to review the current evidence on the clinic applications of GAGs in urology, with particular emphasis on the therapeutic use of hyaluronic acid (HA) and chondroitin sulphate (CS). The major issue in interpreting the available evidence regarding HA-CS is that most of the reported studies are nonrandomized and without a control arm. HA-CS may be considered for further studies, including randomized, controlled trials with adequate power.
GLOBAL CONCEPTS OF BLADDER PAIN SYNDROME (INTERSTITIAL CYSTITIS). Nordling J, Fall M, Hanno P. World J Urol. 2011 Nov 5. [Epub ahead of print]. PMID: 22057291
This article reviews current terminology, diagnostic approaches and treatment. The authors conclude that BPS is no longer considered primarily a bladder disease, but rather one of a number of chronic pain syndromes that is distinguished by being manifest through bladder-related symptoms. A distinct subgroup of patients with Hunner's lesion has specific characteristics, and successful treatment of this subgroup is available.
BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS IN TWIN SISTERS. Tunitsky E, Barber MD, Jeppson PC, Nutter B, Jelovsek JE, Ridgeway B. J Urol. 2012 Jan;187(1):148-52. Epub 2011 Nov 16. PMID: 22088343
In this study bladder pain syndrome scores within twin pairs were moderately correlated, implying some genetic component. Increasing age, irritable bowel syndrome, frequent headaches, drug allergies, self-reported urinary tract infections and physical abuse were factors associated with higher bladder pain syndrome scores.
quality of life
VALIDATION OF A QUALITY-OF-LIFE SCALE FOR WOMEN WITH BLADDER PAIN SYNDROME/INTERSTITIAL CYSTITIS. Bogart LM, Suttorp MJ, Elliott MN, Clemens JQ, Berry SH. Qual Life Res. 2011 Dec 7. [Epub ahead of print]. PMID: 22146841
The aim of this study was to validate a disease-specific scale to measure the impact of symptoms of BPS/IC. Participants for the study were drawn from the RAND Interstitial Cystitis Epidemiology (RICE) Study, a telephone probability survey of 146,231 US households. The authors concluded that the RICE BSI-6 shows excellent internal consistency and strong convergent validity and that it can be used to examine the effects of psychosocial and treatment interventions on QoL among women with BPS/IC.
gender specific pelvic pain
GENDER SPECIFIC PELVIC PAIN SEVERITY IN NEUROGENIC CYSTITIS. Rudick CN, Pavlov VI, Chen MC, Klumpp DJ. J Urol. 2011 Dec 16. [Epub ahead of print]. PMID: 22177208
Rudick et al examined the basis of gender specific pelvic pain in a mouse model of neurogenic cystitis that recapitulates features of IC/PBS and in which pelvic pain is mediated by mast cell histamine. Their findings suggest that pelvic pain in mice with murine neurogenic cystitis is mediated by gender specific responsiveness to mast cells while pelvic pain severity is modulated by genetic factors.
CHILDHOOD SEXUAL TRAUMA IN WOMEN WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME: A CASE CONTROL STUDY. Nickel JC, Tripp DA, Pontari M, Moldwin R, Mayer R, Carr LK, Doggweiler R, Yang CC, Mishra N, Nordling J. Can Urol Assoc J. 2011 Dec;5(6):410-5. doi: 10.5489/cuaj.11110. PMID: 22154637 Free Access
The purpose of this study was to determine and compare the prevalence and impact of childhood traumatic events, with an emphasis on childhood sexual abuse, on patient symptoms, quality of life and other biopsychosocial parameters. None of the findings remained significant in either the IC/BPS or control groups. Early trauma, such as the occurrence of sexual abuse, is associated with some differences in patient adjustment (e.g., pain, quality of life, depression) but this impact appears to be, at most, very modest.
central pain mechanisms
CENTRAL PAIN MECHANISMS IN CHRONIC PAIN STATES - MAYBE IT IS ALL IN THEIR HEAD. Phillips K, Clauw DJ. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):141-54. PMID: 22094191
The authors investigate mechanisms underlying chronic pain which differ from those underlying acute pain. In chronic pain states, central nervous system (CNS) factors appear to play particularly prominent roles. The hallmark of 'centrally driven' pain conditions is a diffuse hyperalgesic state identifiable using experimental sensory testing, and corroborated by functional neuroimaging. The characteristic symptoms of these central pain conditions include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of co-morbid mood disorders. In contrast to acute and peripheral pain states that are responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, central pain conditions respond best to CNS neuromodulating agents, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants.
CONTEMPORARY MANAGEMENT OF THE PAINFUL BLADDER: A SYSTEMATIC REVIEW. Giannantoni A, Bini V, Dmochowski R, Hanno P, Nickel JC, Proietti S, Wyndaele JJ. Eur Urol. 2011 Sep 9. [Epub ahead of print]. PMID: 21920661
Authors critically review and synthesize data from a wide range of current therapeutic approaches to PBS/IC, to quantify the effect size from randomised controlled trials (RCTs), and to reach clinical agreement on the efficacy of treatments for PBS/IC.
They concluded however that limited evidence exists for the few treatments for PBS/IC. The lack of definitive conclusions is due to the great heterogeneity in methods used, assessment of symptoms, duration of treatment, and follow-up in both RCTs and nonRCTs.
SYMPTOM PROFILE VARIABILITY OF INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME BY AGE. Rais-Bahrami S, Friedlander JI, Herati AS, Sadek MA, Ruzimovsky M, Moldwin RM. BJU Int. 2011 Aug 24. doi: 10.1111/j.1464-410X.2011.10481.x. [Epub ahead of print]. PMID: 21883848
Authors conclude that 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, while older patients had higher rates of nocturia, urinary incontinence and Hunner's ulcer disease.
REPEATED VULVOVAGINAL FUNGAL INFECTIONS CAUSE PERSISTENT PAIN IN A MOUSE MODEL OF VULVODYNIA. Farmer MA, Taylor AM, Bailey L, Tuttle AH, Macintyre LC, Milagrosa ZE, Crissman HP, Bennett GJ, Ribeiro-da-Silva A, Binik YM, Mogil JS. Sci Transl Med. 2011 Sep 21;3(101):101ra91. PMID: 21937756
Data show that fungal infection can cause persistent pain long after its resolution and that recurrent yeast infection replicates important features of human provoked vulvodynia in the mouse.
AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Hanno PM, Burks DA, Clemens JQ, Dmochowski RR, Erickson D, Fitzgerald MP, Forrest JB, Gordon B, Gray M, Mayer RD, Newman D, Nyberg L Jr, Payne CK, Wesselmann U, Faraday MM. J Urol 2011 Jun;185(6):2162-70. Epub 2011 Apr 16. PMID: 21497847
A summary of the AUA Guideline for the diagnosis and treatment of IC/BPS. According to the panel, IC/BPS is best identified and managed through use of a logical algorithm as is presented in this Guideline. However, the Panel notes that the most effective approach for a particular patient is best determined by the clinician together with the patient. The Panel emphasises that methods of diagnosis and treatment can be expected to change as the evidence base grows in the future and the strategies presented here will require updating.
depression and panic attacks
Depressive disorders and panic attacks in women with bladder pain syndrome/interstitial cystitis: a population-based sample. Watkins KE, Eberhart N, Hilton L, Suttorp MJ, Hepner KA, Clemens JQ, Berry SH. Gen Hosp Psychiatry 2011 Mar-Apr;33(2):143-9. Epub 2011 Feb 18. PMID: 21596207 This paper from the RAND Corporation reports on the population prevalence of probable depressive disorders and current panic attacks in women with BPS/IC symptoms and describes their characteristics and access to care. The authors suggest that clinicians should be alert to complaints of bladder pain in patients seeking treatment for depressive or anxiety disorders and to complaints of emotional or personal problems in patients seeking treatment for painful bladder symptoms.
Bladder pain syndrome. Hanno P, Nordling J, Fall M. Med Clin N Am 2011;95:55-73 - A useful review of diagnosis and treatment in detail.
Perceptions of "urgency" in women with interstitial cystitis/bladder pain syndrome or overactive bladder. Clemens JQ, Bogart LM, Liu K, et al. Neurourol Urodyn 2010 Nov 5. [Epub ahead of print]. PMID: 21058364 A study comparing urgency symptoms in women with interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB). Urgency symptoms differed in women diagnosed with IC/BPS versus those diagnosed with OAB, but there was significant overlap. This suggests that "urgency" is not a well-defined and commonly understood symptom that can be utilized to clearly discriminate between IC/BPS and OAB. These findings reinforce the clinical observation that it is often challenging to differentiate between these two conditions.
Effects of phenazopyridine on rat bladder primary afferent activity, and comparison with lidocaine and acetaminophen. Aizawa N, Wyndaele JJ. Neurourol Urodyn 2010 Nov;29(8):1445-50. PMID: 20976818 This study explored the effect of phenazopyridine on afferent nerve activity by direct measurement of both Aδ- and C-fibers in the rat, and compared the outcome with the effects of lidocaine (a local anesthetic) and of acetaminophen (an analgesic). It concluded that phenazopyridine can directly inhibit the mechanosensitive Aδ-fibers in the normal rat bladder. This finding might explain its clinical effect in conditions of bladder hypersensitivity.
[CLINICAL AND DIAGNOSTIC EVALUATION IN PATIENTS WITH INTERSTITIAL CYSTITIS][Article in Spanish] Flores-Carreras O, González-Ruiz MI, Martínez-Espinoza CJ, Calderón-Lara SA. Ginecol Obstet Mex 2010 May;78(5):275-80. PMID: 20939238
A useful paper in Spanish concluding that urogynaecologists must consider interstitial cystitis when patients show symptoms of bladder irritability and associated pain with bladder filling. The association of haematuria accompanied by long-term irritability and pain associated with the desire of urination suggests this disease.
[CONTRIBUTION BLADDER BIOPSY TO THE STUDY OF UROGYNAECOLOGICAL PATIENT][Article in Spanish] Flores-Carreras O, Martínez-Espinoza CJ, González-Ruiz MI, Montes-Casillas YE. Ginecol Obstet Mex 2010 Mar;78(3):187-90. PMID: 20939223 This Spanish study supports the practice of bladder biopsy when lesions other than those from chronic infection are observed in the presence of tumours or suspect lesions.
Multifactorial Causes Of Irritating Bladder Symptoms In Patients With Sjögren's Syndrome. Lee KL, Dong CS, Chen MY, Ho CH, Tai HC, Hung SF, Yu HJ. Neurourol Urodyn. 2010 Oct 6. [Epub ahead of print]. PMID: 20928912 Various factors contribute to the irritating bladder symptoms in patients with SS, with DO being predominant. The LUTS developed in patients with SS are not due to any specific single etiology and each patient must be individually carefully evaluated.
Management Strategies for Painful Bladder Syndrome. Lau TC, Bengtson JM. Rev Obstet Gynecol. 2010 Spring;3(2):42-48. PMID: 20842281
- Management of PBS/IC has been a challenge for generations of physicians, owing to a lack of consensus on its definition, an incompletely understood pathophysiology, and numerous available therapies without high-quality evidence to guide their usage.
- This article reviews the most current conception of PBS/IC and data on effective treatments to recommend a management strategy.
Gating of sensory information differs in patients with interstitial cystitis/painful bladder syndrome. Kilpatrick LA, Ornitz E, Ibrahimovic H, Hubbard CS, Rodríguez LV, Mayer EA, Naliboff BD. J Urol. 2010 Sep;184(3):958-63. PMID: 20643444
- Compared to healthy controls, female patients with IC/PBS had decreased ability to adequately filter incoming information and perform appropriate sensorimotor gating. These results suggest that a possible mechanism for altered interoceptive information processing in IC/PBS cases may be a general deficit in filtering mechanisms due to altered pre-attentive processing.
The Overlap of Interstitial Cystitis/Painful Bladder Syndrome and Overactive Bladder. Chung MK, Butrick CW, Chung CW. JSLS 2010 Apr 21. [Epub ahead of print] PMID: 20412643 - this prospective study evaluated the prevalence of positive potassium sensitivity and cystoscopy in patients with overactive bladder
- it was found that many patients with OAB symptoms but little or no pain have cystoscopic evidence of IC/PBS and a positive potassium test
- this suggests that OAB patients who have (partially) failed anticholinergic treatment may benefit from IC/PBS therapies
Development, Validation and Testing of an Epidemiological Case Definition of Interstitial Cystitis/Painful Bladder Syndrome. Berry SH, Bogart LM, Pham C, et al. J Urol 2010 Mar 17. [Epub ahead of print]. PMID: 20303099 - in this RAND Interstitial Cystitis Epidemiology study, a case definition was developed for interstitial cystitis/painful bladder syndrome with known sensitivity and specificity and this definition was compared with other definitions used in epidemiological studies for IC /PBS - it was concluded that no single case definition of interstitial cystitis/painful bladder syndrome provides high sensitivity and high specificity to identify the condition - new definitions have therefore been developed for prevalence studies
Increased nerve growth factor in neurogenic overactive bladder and interstitial cystitis patients. Jacobs BL, Smaldone MC, Tyagi V, et al. Can J Urol 2010;17:4989-94
- urinary NGF levels
were statistically significantly elevated in patients with neurogenic overactive bladder and interstitial cystitis/painful bladder syndrome; urinary NGF levels approached significance in nephrolithiasis patients and levels in patients with bladder cancer were in the range as in those with nephrolithiasis
- the results are difficult to interprete due to the small number of persons in each group: non-diseased urinary tracts (n = 13),
neurogenic overactive bladder (NOAB) (n = 13), idiopathic overactive bladder
(OAB) (n = 17), interstitial cystitis/painful bladder syndrome (IC/PBS) (n = 8),
prostate cancer (n = 7), history of prostate cancer status post robot-assisted
laparoscopic prostatectomy (RALP) (n = 6), active bladder cancer (n = 4), and
nephrolithiasis (n = 4)