Inflammation and central pain sensitization in Interstitial Cystitis/Bladder Pain Syndrome

Central sensitization refers to abnormal pain modulation present which is characterized by non-aversive or mildly aversive stimuli promoting feelings of pain. Many conditions referred to as Functional Somatic Syndromes (FSS)s are characterized by abnormal pain modulation, including pain in areas of the body not thought to be related to the specific FSS with which the patient has been diagnosed. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a diagnosis of exclusion characterized by pelvic pain and urologic symptoms that shares many environmental and psychosocial correlates with FSSs. Treatment is generally non-satisfactory for patients despite substantial healthcare expenditures. Preliminary evidence suggests abnormal pain modulation in IC/BPS. Inflammatory dysregulation is an underexplored mechanism in the pain experience in IC/BPS and FSSs. The purpose of the current project is to explore the role of dysregulated inflammatory processes in IC/BPS with an emphasis on painful symptoms in three distinct papers. Paper one examines the role of inflammation in IC/BPS patients with particular emphasis on the association of Toll-Like Receptor (TLR) - 4 mediated inflammation with symptoms of pelvic pain. Paper two expands on the findings of paper one by exploring the association of TLR-4 mediated inflammation with the presence of comorbid FSSs and widespread pain. Paper three evaluates the predictive ability of these previously explored baseline inflammatory measures by testing the association between TLR-2 and 4-mediated inflammation and diurnal cortisol rhythms with symptom trajectories and symptom flares over one year of observation. Finally, the significance of these novel findings is explored.