Friday, May 16, 2014 1:00 PM-3:00 PM
OCCC: W 307
Urodynamics/Incontinence/Female Urology: Basic Research I
Funding: P20 DK097799
MP1-02: UNDERSTANDING THE MECHANISMS OF VISCERAL ORGAN CROSSTALK: IS IT ALL DUE TO ALTERED PERMEABILITY?
Ehsan Mohammadi*, Karl Tyler, William Dakil, Samuel VanGordon, Beverley Greenwood-Van Meerveld, Robert Hurst, Oklahoma City, OK
Abstract: MP1-02
Introduction and Objectives
Although the pathophysiology of painful bladder syndrome (PBS) is poorly understood there is evidence of female predominance and comorbidity with irritable bowel syndrome (IBS). It is our hypothesis that altered bladder permeability leads to hyperexcitability of visceral afferent neurons and underlies pelvic organ cross sensitization. In this study we aimed to investigate the effect of acute bladder damage on the permeability of the bladder and colon.
Methods
Experiments were performed in anesthetized, ovariectomized (OVX) female Sprague Dawley rats (n = 28); the bladder was catheterized for the intravesical administration of protamine sulfate (1mg/ml in 400 µl) saline-instilled and untreated naïve rats served as controls. After 24 hr. the bladder and colonic tissue were harvested. A sample was taken for histology and the remaining tissue was mounted into modified Ussing chambers and bathed in Kreb’s solution at 37°C. After a stabilization period, permeability was assessed electrophysiologically via transepithelial resistance (TEER) and via the flux of a macromolecular marker (fluorescein isothiocynate-dextrin [FITC-4 KD).
Results
Other than mild edema, exposing the bladder to protamine sulfate induced very minimal physical urothelial damage but no colonic damage as defined histologically. We therefore conclude the main effect was to neutralize the protective glycosaminoglycan layer. However, there was a significant (P<0.01) decrease in TEER in protamine-sulfate treated bladders (1175 ± 164 Ω/cm2) compared to saline-treated (1617 ± 202 1Ω/cm2) or naïve controls (2524 ± 422 Ω/cm2). We also found that in response to mild bladder damage, colonic TEER significantly (P<0.05) decreased (126.7 ± 22.44 Ω/cm2) when compared to saline-treated (177.7 ± 14.23 Ω/cm2) and untreated naïve controls (233.7 ± 14.14 Ω/cm2).
Conclusions
These data demonstrate that following acute bladder damage there is not only an increase in bladder permeability but also a marked rise in the permeability of the colon in the absence of any histological damage to the colon. Thus changes in epithelial permeability may represent a novel mechanism for visceral organ crosstalk and may be important in the overlapping symptomology of PBS and IBS.
Date & Time: May 16, 2014 1:00 PM-3:00 PM
Session Title: Urodynamics/Incontinence/Female Urology: Basic Research I
Sources of Funding: P20 DK097799
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: None
MP16-02: "Getting to Zero": Phenotype, Symptom Severity and Treatment in Chronic Prostatitis/Chronic Pelvic Pain Syndrome Patients Who Self Report Symptom Resolution
Chad Reichard*, Irene Makovey, Daniel Shoskes, Cleveland, OH
Abstract: MP16-02
Introduction and Objectives
The NIH-Chronic Prostatitis Symptom Index (CPSI) was developed to quantify the extent and severity of symptoms in chronic pelvic pain syndrome (CPPS) and impact on quality of life. It is responsive to symptom change and a 6 point drop correlates with perceived patient improvement. Symptom improvement is not equivalent to "cure" and no studies have examined CPSI score targets in patients who consider their CPPS completely resolved. Indeed, there are sufficient non-specific questions in the CPSI that would allow many otherwise normal patients to have a score greater than zero. The aim of this study was to identify a cohort of CPPS patients who considered their symptoms completely resolved and analyze their demographics, clinical phenotype, treatments and CPSI scores.
Methods
We identified 27 CPPS patients seen at our tertiary referral center who at the follow up visits reported that they felt their symptoms to be completely resolved ("cured"). Demographics, UPOINT phenotypes, treatments, and pre and post CPSI scores were examined. We also compared these variables to an existing database of 220 CPPS patients previously evaluated and phenotyped at our clinic.
Results
Patients ranged in age from 22 to 68 years. Median follow up was 11 months (range 3 to 73 months). There were a median of 3 UPOINT domains positive (range 1-5) and a median of 3 treatments prescribed (range 1-6). UPOINT positive domains were 67% urinary, 26% psychosocial, 63% organ specific, 11% infectious, 26% neurologic, and 70% musculoskeletal tenderness. Mean change in CPSI subscores before and after therapy were pain 9.7 to 3.0, urinary 3.6 to 1.2, QOL 8.1 to 2.4, and total 21.4 to 6.7 (all p<0.0001). Of note, only 5 (19%) patients reported a total score of 0. Comparing this "cured" group to a previously published cohort of phenotyped CPPS patients, the "cured" group had lower starting total and pain CPSI scores (21.4 vs 25.0 p=0.008; 9.7 vs 11.5 p=0.02 respectively). There were no differences in number of UPOINT domains, age or proportion of positive domains between the two data sets.
Conclusions
Many men with CPPS can reach a subjective cure, however having done so, the majority do not reach a CPSI score of 0. This group of "cured" patients is similar to our typical tertiary referral cohort in terms of age and phenotype but differs in having slightly lower starting CPSI pain scores.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: None
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: none
MP16-03: Pelvic-floor based Physical Therapy Treatment for Chronic Orchalgia
Erin Glace*, Virginia Beach, VA, Courtney Anderson, Jack Zuckerman, Kurt McCammon, Norfolk, VA
Abstract: MP16-03
Introduction and Objectives
Chronic orchalgia is a common problem presenting to the urologist. Recent research and treatment has begun to focus on musculoskeletal dysfunction as a major contributor to this type of pelvic pain. We observed in our pelvic floor-based physical therapy (PFPT) program a reduction in patient reported pain following a comprehensive physical therapy treatment regimen. Here, we assess the clinically reported outcomes of patients in our center that presented with orchalgia who underwent physical therapy.
Methods
A retrospective chart review was conducted on men presenting with a chief complaint of unilateral or bilateral orchalgia between January 2009 and April 2013 who were subsequently referred for PFPT. Referrals to physical therapy were made after evaluation ruled out pathologic etiologies for the orchalgia. Patients were evaluated and treated by our physical therapy team according to patient specific musculoskeletal impairments. Treatment included pelvic alignment exercises, therapeutic stretching and strengthening, manual therapy, modalities and EMG biofeedback. Following treatment, a global response measure was assessed based on patients’ self-reports of pain reduction. Additionally, a follow-up phone survey was conducted to assess the perceived degree of pain at various intervals after completion of physical therapy.
Results
We identified 61 patients that met inclusion criteria. After a mean 4.9 months of PFPT, 86.9% indicated their testicular pain was better, 13.1% reported no change and 0% reported worsening of their pain. Univariate analysis demonstrated that patient age, duration of symptoms, laterality and number of therapy sessions were not predictive of improvement following physical therapy. Thirty-two of the 61 patients participated in the follow up phone survey. Of these patients, 87.5 % reported a sustained improvement in their testicular pain, at an average of 7 months after completion of physical therapy.
Conclusions
Physical therapy represents a reasonable treatment option for many patients suffering from testicular pain. Symptom improvement was achieved in a large majority of our patients following PFPT and the results appear to be durable. Larger studies with longer follow up are needed.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: none
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: none
MP16-05: Eviprostat has an identical effect compared to pollen extract (Cernilton) in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study
Atsushi Imai*, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama, Atsushi Kyan, Nobuyoshi Takahashi, Toshiaki Kawaguchi, Shinya Takahashi, Yuji Yagihashi, Keiya Miki, Hirosaki-shi, Japan
Abstract: MP16-05
Introduction and Objectives
Previously reported results of a prospective, randomized placebo-controlled study showed that the pollen extract (Cernilton) significantly improved total symptoms, pain, and quality of life in patients with inflammatory prostatitis/chronic pelvic pain syndrome (CP/CPPS) without severe side effects (Wagenlehner FM et al, Eur Urol, 2009). A phytotherapeutic agent, Eviprostat, is reportedly effective in a rat model of nonbacterial prostatitis (Sugimoto M et al, Prostate, 2011). The aim of the present study was to compare the efficacy and safety of Eviprostat to that of the pollen extract in the management of CP/CPPS.
Methods
The patients with category III CP/CPPS were randomized to receive either oral capsules of Eviprostat (two capsules, q 8 h) or the pollen extract (two capsules, q 8 h) for 8 weeks. The primary endpoint of the study was symptomatic improvement in the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). Participants were evaluated using the NIH-CPSI and the International Prostate Symptom Score (IPSS) at baseline and after 4 and 8 weeks.
Results
In the intention-to-treat analysis, 100 men were randomly allocated to Eviprostat (n = 50) or the pollen extract (n = 50). Response (defined as a decrease in the NIH-CPSI total score by at least 25%) in the Eviprostat group and the pollen extract group was 88.2% and 78.1%, respectively. There was no significant difference in the total, pain, urinary, and quality of life (QOL) scores of the NIH-CPSI. between the two groups at 8 weeks. This was also the case with the total, voiding, and storage symptoms of the IPSS. There were no adverse events observed in any patients in this study.
Conclusions
Both the pollen extract and Eviprostat significantly reduced the symptoms of category III CP/CPPS without any adverse events. Eviprostat has an identical effect on category III CP/CPPS compared the pollen extract.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: none
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: None
MP16-06: Clinical efficacy of roxithromycin in men with chronic prostatitis/chronic pelvic pain syndrome in comparison with ciprofloxacin and aceclofenac: A prospective, randomized, multicenter pilot trial
Hyun-Sop Choe*, Hee-Youn Kim, Dong-Sup Lee, Seung-Ju Lee, Suwon, Korea, Republic of, Chang-Hee Han, Uijeongbu, Korea, Republic of, Bong-Suk Shim, Yong-Hyun Cho, Seoul, Korea, Republic of
Abstract: MP16-06
Introduction and Objectives
Roxithromycin is effective in the treatment of intracellular organisms, including chlamydia and mycoplasma, and exhibits anti-inflammatory and immunomodulatory effects on respiratory diseases. To explore the potential therapeutic benefit of roxithromycin in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), this study compared the effect of roxithromycin with ciprofloxacin and aceclofenac.
Methods
A total of 75 patients with CP/CPPS were randomized to three groups in open-label: group 1, ciprofloxacin; group 2, aceclofenac; and group 3, roxithromycin. The patients were treated for 4 weeks and were subsequently followed for 12 weeks. Changes from baseline in the total and domain scores of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) were evaluated.
Results
The NIH-CPSI score decreased in the roxithromycin, ciprofloxacin, and aceclofenac groups to a similar degree. The NIH-CPSI initial and 12-week total scores were 20.3 and 10.0, respectively, in group 1; 23.6 and 14.3, respectively, in group 2; and 21.1 and 9.8, respectively, in group 3. The three treatment arms did not differ significantly with respect to the efficiency of treatment (p > 0.05). Compared to patients in groups 1 and 2, group 3 patients with Category IIIb disease exhibited favorable results upon follow-up 12 weeks after treatment. The International Prostate Symptom Score (IPSS), uroflowmetry, and post void residual volume were equivalent between the groups.
Conclusions
Roxithromycin exhibits similar or favorable effects on the improvement of CP/CPPS compared to ciprofloxacin and aceclofenac. Roxithromycin could be used as a new therapeutic agent for CP/CPPS. Further study of the immunomodulatory action of roxithromycin in CP/CPPS is required.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: None
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316)
MP16-08: Search for Microorganisms in Men with Urologic Chronic Pelvic Pain Syndrome: A Culture-Independent Analysis of Cases and Controls Enrolled in the trans-MAPP Epidemiology/Phenotyping (EP) Study
J. Curtis Nickel*, Kingston, Canada, Alisa Stephens, Philadelphia, PA, Jun Chen, Boston, MA, Richard Landis, Philadelphia, PA, Christopher Mullins, Bethesda, MD, Garth Ehrlich, Philadelphia, PA, The MAPP Research Network, Bethesda, MD
Abstract: MP16-08
Introduction and Objectives
We hypothesized that differences in lower urinary tract microbial populations between male UCPPS patients and normal subjects may be implicated in the etiology of male UCPPS. We used novel state-of-the-art culture-independent methodology to compare the microbiota of the lower urinary tract in men with UCPPS and controls enrolled in the NIH trans-MAPP EP study.
Methods
Each participant (cases and non-UCPPS controls) were asked to provide initial (VB1), midstream (VB2) and post-prostatic massage (VB3) urine specimen. Specimens were analyzed with Ibis T-5000 Universal Biosensor technology which employs a polymerase chain reaction – electron spray ionization – time-of-flight – mass spectoscopic- based system to provide comprehensive identification of all bacterial species. Differences between UCPPS patients and controls in the presence of species or the number of different species within a higher level group were tested using PERMANOVA, and Fisher’s Exact test. All tests were conducted at the species, genus,and gram-stain level.
Results
417 male subjects (191 cases; 226 controls) were enrolled in the trans-MAPP-EP study. Baseline VB1 and VB2 urine specimens were obtained from 110 UCPPS cases and 115 matched controls (subjects with no UCPPS symptoms). VB3 samples were provided by 67 CP/CPPS and 62 controls. A total of 78, 73 and 54 species (42, 39 and 27 genera) were detected in VB1, VB2 and VB3 respectively. Mean (SD) VB1, VB2 and VB3 species count per person was 1.62 (1.28), 1.38 (1.36) and 1.33(1.24) for cases and 1.75(1.32), 1.23(1.15) and 1.56 (0.97) for controls respectively. Overall species and genus composition significantly differed between UCPPS patients and controls in VB1 only (p=0.008 species level, p=0.011 genus level, p=0.079 Gram-stain level) with overall differences driven by B. cenocepacia (RR=3.34, p=0.009), P. acnes (RR 0.38, p=0.01), and S. capitis/capare (RR=0.17, p=0.008). These differences (and similar trends at genus level) remained significant after adjustment for multiple comparisons. No significant differences were observed at the Gram-stain level in VB1 or at any level in VB2 or VB3.
Conclusions
While our results make it difficult to implicate the minor differences in lower urinary tract microbiota (VB1 only) in patients vs controls for a role in the etiology and pathogenesis of UCPPS in males, further work is required to determine if microbial composition or fluctuations influence symptom patterns over time.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (DK82370, DK82342, DK82315, DK82344, DK82325, DK82345, DK82333, and DK82316)
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: none
MP16-09: TRUS Characteristics Of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Comparison With Age-Matched Controls
Dorit Zilberman*, Ramat-Gan, Israel, Matvet Tsivian, Durham, NC, Yoram Mor, Gil Raviv, Ramat Gan, Israel
Abstract: MP16-09
Introduction and Objectives
We sought to explore the yield of trans-rectal ultrasound (TRUS) in cases of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).
Methods
The records of all patients, who were referred for TRUS due to CP/CPPS, were retrospectively reviewed. Digital rectal exam (DRE) was performed before TRUS. The following parameters were recorded: prostate length; width; height; volume; external border; peripheral zone (PZ); transitional zone (TZ); TZ/PZ border; seminal vesicle (SV); presence of median lobe; dilation of vas deferens (VD) or ejaculatory duct (ED); presence of significant post-void residual (PVR). Data were compared to an age-matched control group that had undergone the same imaging for other reasons.
Results
Between the years 2004-2012, 216 patients aged 42 years (35-50) underwent DRE and TRUS by a single operator. Per DRE, their prostates appeared smaller (15.5 cc vs. 25 cc, p<0.001) and less suspicious compared with the control group (3.2% vs. 9.3%, p=0.016). Differences seen in TRUS between the study and the control groups, respectively, were as follows: less irregularities and less hypoechoic areas in the PZ (p<0.001); less cystic spaces and less median lobes in the TZ (p=0.008, p=0.001, respectively); less ED dilation (5.1% vs. 11.6%, p=0.02); more calcifications (51.4% vs. 38%, p=0.007); more VD dilation (19.1% vs. 11.6%, p=0.044); more periurethral vascularity (2.8% vs. 0%, p=0.03). No differences were seen in SV parameters and in PVR.
Conclusions
TRUS for CP/CPPS, albeit different compared to age-matched controls, has no pathognomonic findings. Therefore, for this entity it has very little yield.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: none
Saturday, May 17, 2014 1:00 PM-3:00 PM
OCCC: W 314
Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Funding: NIH: 1R01DK083609-01A2, 1R01DK094898-01A1
MP16-17: IL7, a primary mediator of T-cell differentiation, is correlated with pain in both CPPS patients and experimental autoimmune prostatitis (EAP) in mice.
Stephen Murphy*, Joesph Done, Praveen Thumbikat, Anthony Schaeffer, Chicago, IL
Abstract: MP16-17
Introduction and Objectives
The etiology of chronic pelvic pain syndrome (CPPS) is unknown but is thought to involve pro-inflammatory and autoimmune mechanisms. Previous investigations have highlighted a role for mediators of inflammation in disease progression by correlating levels of certain cytokines and chemokines with patient score. While these are informative in delineating the drivers of pathology, little has been done to demonstrate their role in causation. Mouse models of CPPS have been developed to attempt to understand the mechanism of these biomarkers in driving pain in humans. Here using both patient samples and the murine EAP model of CPPS we identify a novel cytokine that is increased in patients compared to controls and is associated with increased pain. This cytokine, namely IL7, is fundamental to the development of mature T-cell subsets and has roles in the disease pathogenesis of multiple sclerosis. It has also been identified as a key player in coordinating the maturation of auto-reactive T-cells, which can result in chronic autoimmunity. These findings highlight the role of T-cells in driving pain and indicate that differentiation and activation of lymphocytes may be key to development of autoimmunity.
Methods
A multiplex cytokine array was performed using EPS samples from 33 patients and 8 controls. Levels of 41 chemokines and cytokines were assayed and total protein differences calculated. A combination of linear regression and correlation analyses was used to compare levels of cytokine with increasing levels of pain, urinary, QOL and Total scores, as assessed by NIH-CPSI questionnaire. Data from this study was then confirmed in murine EAP by QRTPCR, western and IHC staining.
Results
Analysis of EPS samples from patients and controls revealed increases in levels of IL7, TNFa and GRO-a. Linear regression and correlation analysis revealed a positive association with increased levels of IL7 and pain, urinary, QOL and total scores and a negative correlation between decreased IL1RA levels and only QOL and Total scores. These results were mirrored in the murine EAP model in C57BL/6 mice. By QRTPCR we show increased IL7 in prostate and iliac lymph node tissue but not in bladder or spleen. Patient data was also confirmed at the protein level by IHC and western.
Conclusions
The T-cell differentiation factor IL7 is increased in patient EPS samples and these increased levels are correlated with increased pain, in both patients and murine models. These findings highlight the fundamental role of T-cell development in mediating pain in CPPS.
Date & Time: May 17, 2014 1:00 PM-3:00 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Prostate & Genitalia
Sources of Funding: NIH: 1R01DK083609-01A2, 1R01DK094898-01A1
Saturday, May 17, 2014 3:30 PM-5:30 PM
OCCC: W 312
Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Funding: NIH/NIDDK
PD9-03: Inflammatory Biomarkers are Associated with Co-Morbid Pain Conditions in UCPPS Patients: a MAPP Study
Catherine Bradley*, Andrew Schrepf, Susan Lutgendorf, Michael O'Donnell, Yi Luo, Karl Kreder, Iowa City, IA
Abstract: PD9-03
Introduction and Objectives
Urological Chronic Pelvic Pain Syndromes (UCPPS), including Interstitial Cystitis/Bladder Pain Syndrome and Chronic Prostatitis, frequently co-occur with other pain syndromes (Non-Urological Associated Syndromes (NUAS)). Systemic inflammatory dysregulation, including altered cytokine levels and responses associated with toll-like receptor (TLR) stimulation, has been identified in other pain conditions, and we hypothesize may be involved in the wider-spread pain seen in UCPPS patients with NUAS. The objective of this study was to determine if inflammatory cytokine responses differ among UCPPS patients with and without NUAS.
Methods
UCPPS patients enrolled in the Multidisciplinary Approach to Pelvic Pain (MAPP) multicenter Epidemiologic Phenotyping Study were eligible for this single-site study. Demographics, questionnaires and plasma were collected. Inflammatory cytokines were assayed using ELISA in plasma and in TLR2- and TLR4-stimulated peripheral blood mononuclear cells (PBMC). NUAS (irritable bowel syndrome (IBS), vulvodynia, chronic fatigue syndrome (CFS), temporomandibular joint disorders (TMJ) and fibromyalgia (FM) were identified using self-reported symptoms and standard diagnostic criteria. Patient characteristics and biomarker results were compared in UCPPS patients with and without NUAS using ANOVA and chi-squared tests. General Linear Models, adjusting for BMI, were used to test UCPPS patient group main effects, sex and interactions on cytokine results.
Results
72 UCPPS patients were included (58 F, 14 M), including 34 UCPPS only and 38 UCPPS + NUAS (IBS (27), FM (2), CFS (8), TMJ (21) and vulvodynia (13)). Age, education, income, race and ethnicity were similar between groups. UCPPS + NUAS patients had greater symptom severity based on Interstitial Cystitis Symptom Index scores (11.6 vs. 8.2, p<0.001), but similar Genitourinary Pain Index scores, compared to UCPPS only patients. UCPPS + NUAS patients had higher plasma IL-6 (p=.03) but not higher CRP. TLR4-stimulated IL1-β was elevated in UCPPS + NUAS patients compared to UCPPS only (p=.01); TLR4 stimulated IL-6 and TLR2-stimulated cytokine production did not differ between groups. Cytokine responses did not differ between men and women.
Conclusions
Compared to patients with UCPPS only, UCPPS patients with NUAS have higher plasma IL-6 and greater cytokine responsivity to TLR4 stimulation in PBMC. These findings suggest inflammation and inflammatory responsivity may play a role in the development of broader pain syndromes.
Date & Time: May 17, 2014 3:30 PM-5:30 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Sources of Funding: NIH/NIDDK
Saturday, May 17, 2014 3:30 PM-5:30 PM
OCCC: W 312
Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Funding: U01 DK082342
PD9-04: Receptor Cascade Mediating Post-UTI Chronic Pain
John Rosen, Kansas City, KS, David Klumpp*, Chicago, IL
Abstract: PD9-04
Introduction and Objectives
E. coli evoke a spectrum of pain responses when instilled into the bladder, ranging from no pelvic pain to post-UTI chronic pain that persists after transient infection. Previous studies indicate that E. coli-induced pain is mediated by TLR4 independent of inflammation. Here, we evaluated the hypothesis that TRPV1 and/or CCR2 mediators of post-UTI chronic pain downstream of TLR4.
Methods
Post-UTI chronic pain was evaluated in mice by tactile allodynia in response to von Frey filaments applied to the pelvic region. Viscero-motor reflex (VMR) of abdominal muscles in response to bladder distension with saline was used as an independent measure of visceral pain. Anxiety-like/depression-like behavior was quantified as a central manifestation of chronic pain using novelty-suppressed feeding (NSF).
Results
Mice infected with E. coli strain S[phi]874 acquired chronic pelvic allodynia that persisted long after bacterial clearance. Treatment with the TRPV1 antagonist capsazepine at the time of infection signficantly inhibited the development of chronic allodynia. In contrast, capsazepine administered after the onset of chronic allodynia had no effect, and these allodynia findings were corroborated at the levels of VMR activity and NSF. Similarly, allodynia and VMR activity did not develop in TRPV1-deficient mice infected with S[phi]874. Induction of MCP-1 and CCR2 was noted in sacral DRGs, and administration of a CCR2 antagonist significantly reduced allodynia.
Conclusions
These data suggest that TRPV1 mediates the establishment of chronic pelvic pain in response to a transient E. coli infection but is not required for pain maintenance. Conversely, CCR2 is required for maintenance of post-UTI chronic pain. Together with previous studies, our data suggest that E. coli may induce chronic pelvic pain through a cascade of TLR4-TRPV1-CCR2 in the periphery.
Date & Time: May 17, 2014 3:30 PM-5:30 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Sources of Funding: U01 DK082342
Saturday, May 17, 2014 3:30 PM-5:30 PM
OCCC: W 312
Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Funding: None
PD9-12: What Generates Pain Catastrophizing in IC/BPS?
Dean A. Tripp*, J. Curtis Nickel, Laura Katz, Kingston, Canada, Lesley K. Carr, Toronto, Canada, Robert Mayer, Rochester, NY
Abstract: PD9-12
Introduction and Objectives
IC/BPS is a chronic pelvic pain syndrome associated with pain, urological symptoms and disability, largely unresponsive to medical treatment. Catastrophizing is a well-established predictor of pain and pain-related outcomes in IC/BPS, but the mechanisms and predictors of catastrophizing in IC/BPS remain unknown. Illness perceptions have been identified as important precursors to appraisals and coping mechanisms, and remain unexamined for chronic pelvic pain. The aim of this study was to evaluate illness perceptions as a predictor of patient catastrophizing within a biopsychosocial model.
Methods
Female patients with IC/BPS (n=70) were recruited from tertiary care urology clinics and completed questionnaires (demographics, O’Leary Sant, McGill Pain Questionnaire, Brief-Illness Perceptions Questionnaire, Pain Catastrophizing Scale). Bivariate zero-order correlations were run between variables to assess for multicollinearity. Hierarchical multivariable regression analyses were run in the prediction of pain catastrophizing and its subscales.
Results
Patients ranged in age from 20-85 years (mean=51.51±17.25), were predominantly Caucasian (94.3%), having at least some university / college education (78.6%), and a mean length of diagnosis of 8.44±9.92 years. In step 1 of the regression, demographics (age, education and length of diagnosis) did not predict catastrophizing. In step 2, pain (β=0.32, p=0.01) and IC problems (β=0.25, p=0.05) were both significant predictors of catastrophizing (F=9.92, p<.001). In step 3, illness perceptions (β=0.49, p<0.001) was the lone predictor of catastrophizing (F=13.10, p<.001), over and above demographics, pain and IC symptoms/problems. In further sub-analyses, emotional illness perceptions (e.g., concern about illness, and emotional impact of illness) mediated the relationship between pain/symptoms and helplessness catastrophizing.
Conclusions
Illness perceptions (e.g., emotional) were significant in predicting helplessness catastrophizing in a biopsychosocial model. Understanding the precursors and mechanisms of catastrophizing is important, as recent research has shown that catastrophizing is amenable to change with psychological intervention in chronic pelvic pain (Tripp et al., 2011). Further understanding this relationship can help to improve patient interventions in order to decrease disability and improve IC/BPS quality of life.
Date & Time: May 17, 2014 3:30 PM-5:30 PM
Session Title: Infections/Inflammation of the Genitourinary Tract: Interstitial Cystitis
Sources of Funding: None
Sunday, May 18, 2014 10:40 AM-12:00 PM
OCCC:
Plenary I - Sunday
Funding: This research was supported by: NIH grants 1R01DK100974-01 (to J.K. and J.A.), ICA Pilot grant and the Fishbein Family IC Research Foundation/Interstitial Cystitis Association; New York Academy of Medicine; and Children’s Hospital Boston Faculty Development (to J.K.). J.K. is an American Urological Association Foundation Research Scholar and an Eleanor and Miles Shore Scholar of Harvard Medical School.
PI-02: Late-Breaking Abstract: Urinary Metabolite Profiling Combined with Computational Analysis Suggest Interstitial Cystitis-Associated Candidate Biomarkers
Jayoung Kim*, Los Angeles, CA
Abstract: PI-02
Introduction and Objectives
Interstitial cystitis/painful bladder syndrome/bladder pain syndrome (IC), a chronic syndrome of unknown etiology, is a bladder disease based on variable symptoms such as pelvic and/or perineal pain, discomfort, urinary frequency, and urgency. The lack of convenient biomarkers and a poor understanding of mechanism of IC have challenged disease diagnosis and therapy. The goals of this study are to identify non-invasive biomarker candidates and to gain new insight into disease mechanisms suggesting objective, clinically relevant indicators of the disease that might be employed clinically.
Methods
We carried out a global metabolomics analysis of urine from IC patients (n=45) and from the matched controls (n=19) recruited in Inha University in South Korea using an NMR spectrometer. To analyze NMR spectra, we applied the Chenomx NMR Suite, and performed a multi-step analysis including a nonparametric Wilcoxon Rank Sum test and analysis using MetaboAnalyst version 2.0.
Results
Principal component analysis (PCA) and orthogonal projections to latent structure-discrimination analysis (OPLS-DA) suggested that metabolites from IC and controls were clearly separated. 140 metabolites whose urinary levels were significantly changed in IC patients (p>0.05), as compared to controls, and eight metabolite peaks were identified as the strongest signature of IC with strong correlation score (>80 coefficients). Three of peaks (2.924, 3.2485, and 3.243) were annotated as tyramine, the pain-related neuromodulator. Two of them (3.0212 and 3.0157) were 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly upregulated in urine specimens from IC, suggesting that tyramine and 2-oxoglutarate as potential non-invasive biomarkers for patients with IC.
Conclusions
In this study, we identify non-invasive classifiers that can discriminate IC patients from controls. This finding can be the basis for one or more prospective clinical trials and thus has direct relevance to human health and patient care.
Date & Time: May 18, 2014 10:40 AM-12:00 PM
Session Title: Plenary I - Sunday
Sources of Funding: This research was supported by: NIH grants 1R01DK100974-01 (to J.K. and J.A.), ICA Pilot grant and the Fishbein Family IC Research Foundation/Interstitial Cystitis Association; New York Academy of Medicine; and Children’s Hospital Boston Faculty Development (to J.K.). J.K. is an American Urological Association Foundation Research Scholar and an Eleanor and Miles Shore Scholar of Harvard Medical School.
