Inflammatory Biomarkers are Associated with Co-Morbid Pain Conditions in UCPPS Patients: a MAPP Study

Bradley CS, Schrepf A, Lutgendorf S, O'Donnell M, Luo Y, Kreder K. Inflammatory Biomarkers are Associated with Co-Morbid Pain Conditions in UCPPS Patients: a MAPP Study. Paper presented at: American Urological Association Annual Meeting; 2014 May 17; Orlando, FL.

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- 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.