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Papers of the Week

Papers: 1 Apr 2023 - 7 Apr 2023

Psychology, Translational

Human Studies, Molecular/Cellular, Neurobiology

Abdominal/Pelvic Pain, Psychological/Comorbidities

2023 Mar 29

Brain Behav Immun


Early and Recent Exposure to Adversity, TLR-4 Stimulated Inflammation, and Diurnal Cortisol in Women with Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Research Network Study.


Lutgendorf SK, Zia S, Luo Y, O'Donnell M, van Bokhoven A, Bradley CS, Gallup R, Pierce J, Taple BJ, Naliboff BD, Clemens JQ, Kreder KJ, Schrepf A


Both early (ELA) and recent life adversity (RLA) have been linked with chronic pain conditions and persistent alterations of neuroendocrine and inflammatory responses. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic urologic disorder characterized by bladder and/or pelvic pain, and excessive urinary frequency and/or urgency. IC/BPS has been associated with high levels of ELA as well as a distinct inflammatory signature. However, associations between ELA and RLA with inflammatory mechanisms in IC/BPS that might underlie the link between adversity and symptoms have not been examined. Here we investigated ELA and RLA in women with IC/BPS as potential risk factors for inflammatory processes and hypothalamic-pituitary-adrenal (HPA) abnormalities using data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. Women with IC/BPS and healthy controls (n=154 and 32, respectively) completed surveys, collected salivary cortisol at awakening and bedtime for 3 days, and gave a blood sample which was analyzed for 7 LPS-stimulated cytokines and chemokines (IL-6, TNFα, IL-1β, MIP1α, MCP1, IL-8, and IL-10). Two cytokine/chemokine composites were identified using principal components analysis. Patients with greater exposure to RLA or cumulative ELA and RLA of at least moderate severity showed elevated levels of a composite of all cytokines, adjusting for age, body mass index, and study site. Furthermore, there was a trending relationship between ELA and the pro-inflammatory composite score. Nocturnal cortisol and cortisol slope were not associated with ELA, RLA, or inflammation. The present findings support the importance of adverse events in IC/BPS via a biological mechanism and suggest that ELA and RLA should be assessed as risk factors for inflammation as part of a clinical workup for IC/BPS.