Date of Degree
PhD (Doctor of Philosophy)
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.
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition that affects many women in the United States. The primary symptoms are frequent and urgent urination accompanied by pain. It is not currently known what causes IC/BPS and this makes treating the condition difficult. IC/BPS is known to be associated with greater sensitivity to pain. The purpose of these research projects is to determine if painful symptoms in IC/BPS are associated with different aspects of the immune system that control a broad process known as inflammation.
The first project of this research project examined differences in inflammatory processes between women with IC/BPS and a healthy comparison group. Women with IC/BPS displayed distinct differences: higher levels of inflammation, different patterns of inflammation-controlling hormones, and greater inflammation responses by immune cells challenged with immune-stimulating substances. These responses were associated with the level of pain reported by women with IC/BPS. The second project examined IC/BPS patients with and without other pain conditions; inflammation responses were associated with having other pain conditions, more widespread pain, and greater sensitivity to painful pressure. The third project examined IC/BPS symptoms over 48 weeks; inflammation responses at baseline were associated with less symptom improvement.
These findings suggest that IC/BPS is marked by altered inflammation, and these alterations are associated with painful symptoms. It is possible that inflammation plays a role in the development of IC/BPS and greater sensitivity to pain. These findings may help to identify patients that could benefit from systemic anti-inflammatory treatments.
x, 99 pages
Includes bibliographical references (pages 85-99).
Copyright 2015 Andrew David Schrepf