Summary: Inflammatory dysregulation marks interstitial cystitis/bladder pain syndrome. Inflammatory responses in peripheral blood mononuclear cells following Toll‐like receptor 4 stimulation predict the magnitude of painful symptoms.
ABSTRACT: Toll‐like receptors (TLR) are known to play a role in chronic pain, from animal models and limited research in humans, but their role in interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown. Similarly, alterations of the hypothalamic–pituitary–adrenal axis have been reported in some pain conditions. Our objectives were to identify inflammatory processes that might distinguish individuals with IC/BPS from healthy controls (HC) and to examine their associations with IC/BPS symptoms. Female participants (58 IC/BPS patients and 28 HCs) completed pain and urinary symptom questionnaires and collected saliva for cortisol as part of the Multidisciplinary Approach to Pelvic Pain study. Inflammatory cytokines were assayed in plasma, and in TLR‐2− and TLR‐4–stimulated peripheral blood mononuclear cells. Controlling for BMI and negative affect, between‐group differences were analyzed by general linear models, and relationships between symptoms and inflammatory variables were analyzed by regression. Compared to HCs, IC/BPS patients had higher levels of plasma interleukin‐6 (P = .040), greater interleukin‐1β responsive to TLR‐2 stimulation (P = .040), and flatter diurnal cortisol slopes (P = .010), indicating inflammatory dysregulation. In IC/BPS patients, inflammation after TLR‐4 stimulation was associated with multiple symptoms, including genitourinary pain (P = .010), sexual pain (P = .002), and marginally with urinary symptoms (P = .068). Genitourinary pain severity (P = .008), frequency (P = .001), and pain with intercourse (P = .002) were strongly associated with TLR‐4 inflammatory response. TLR‐4 appears to play a central role in painful symptoms of IC/BPS patients, which may be linked to poor endogenous inflammatory control. These findings may help to identify new mechanisms in IC/BPS and lead to new therapeutic approaches.
aDepartment of Psychology, University of Iowa, Iowa City, IA, USA
bDepartment of Urology, University of Iowa, Ames, IA, USA
cDepartment of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA
*Corresponding author at: Department of Psychology, University of Iowa, E11 Seashore Hall, Iowa City, IA 52242, USA. Tel.: +1 (319) 335 2432.
Submitted April 22, 2014; revised May 19, 2014; accepted May 29, 2014.
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