Inflammation and Symptom Change in Interstitial Cystitis or Bladder Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study

Abstract

Objective To explore inflammatory factors that influence symptom changes in interstitial cystitis/bladder pain syndrome (IC/BPS). This longitudinal, prospective study examined the association of inflammation elicited by Toll-Like Receptor (TLR) stimulation in peripheral blood mononuclear cells (PBMCs) and diurnal cortisol rhythms with changes in painful and urinary symptoms of IC/BPS and symptom flares over a 48 week period. Materials and Methods Participants were 24 women meeting criteria for IC/BPS who supplied blood for isolation of PBMCs and three days of salivary cortisol samples prior to a baseline visit. Participants completed the Genitourinary Pain Index (pain and urinary subscales) and reported symptom flares every 2 weeks for 48 weeks. Mixed effects longitudinal and regression models were used to determine if inflammatory variables were associated with the changes in IC/BPS symptoms (Time × variable interactions), and the probability of a symptom flare. Results Elevated TLR-4 inflammation (p = .031) and elevated TLR-2 inflammation (p = .045) from PBMCs, and flattened diurnal cortisol slope (p = .012) were each associated with less improvement in genitourinary pain over time. Additionally, elevated TLR-4 inflammation was associated with less improvement in urinary symptoms (p = .018) while TLR-2 inflammation and cortisol slope were not (both p > .16). In contrast, no inflammatory measure was associated with an increased likelihood of reporting a symptom flare (all p > .25). Conclusions TLR-mediated inflammation and diurnal cortisol slope may be useful as markers of symptom changes in IC/BPS.

Clinical and Psychosocial Predictors of Urological Chronic Pelvic Pain Symptom Change in 1 Year: A Prospective Study from the MAPP Research Network

“…These include the Physical Health component of the SF-12 quality of life measure along with the PROMIS Sleep and Fatigue scales. Taken together with recent studies showing poorer outcome associated with increased inflammatory markers in UCPPS 27 and altered HPA axis function in CP 28 , this data suggest inflammatory processes as part of an overall stress response may be a part of the ‘centralization’ mechanisms involved in UCPPS, perhaps recursively as both a driver and responder to peripheral events. Future MAPP analyses of inflammatory markers and brain imaging will be critical to test these potential mechanisms.…”

Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study

“…Inflammation plays a central role in the pathogenesis of IC/BPS and may directly affect bladder function in IC/BPS patients [ 25 ]. Our recent studies supported the fundamental role of inflammation in IC/BPS, as the production of Toll-like receptor 4 (TLR4) mediated proinflammatory cytokines IL-1ß and IL-6 was significantly associated with multiple IC/BPS pain indicators [ 26 – 28 ]. As a clinically relevant model, the URO-MCP-1 model develops bladder inflammation and functional changes such as pelvic pain, urinary frequency and urgency.…”

Psychology of Chronic Pelvic Pain: Prevalence, Neurobiological Vulnerabilities, and Treatment

“…62 Work in women with IC/BPS shows parallels to this phenomenon, as women with IC/BPS show heightened inflammatory responses when their monocytes/lymphocytes are isolated and stimulated with a TLR-2 agonist. 63 Furthermore, when these same cells are stimulated with a TLR-4 agonist, the subsequent response predicts the degree of widespread pain, genitourinary pain severity, and dyspareunia. 63,64 A recent review considers the evidence for TLRs and inflammatory sensitization pathways in visceral pain with a special emphasis on the high female preponderance of these conditions.…”

“…63 Furthermore, when these same cells are stimulated with a TLR-4 agonist, the subsequent response predicts the degree of widespread pain, genitourinary pain severity, and dyspareunia. 63,64 A recent review considers the evidence for TLRs and inflammatory sensitization pathways in visceral pain with a special emphasis on the high female preponderance of these conditions. 65 Beyond their role in pain, TLRs appear to play potentially important roles in mood disorders.…”