Role of hemopexin in the development of urologicchronic pelvic pain syndrome - PROJECT SUMMARY/ABSTRACT Urologic chronic pelvic pain syndrome (UCPPS) is a condition characterized by persistent pelvic pain and lower urinary tract symptoms (LUTS) and has an incompletely understood etiology. The symptomology of UCPPS is often differentially attributed to the urinary bladder in females and the prostate in males. Two important factors that have been associated with both the development of UCPPS and symptom flares in patients are chronic stress and dysregulation of extracellular heme homeostasis. The objective of this application is to examine the role of hemopexin (Hpx) in pelvic and visceral pain associated with UCPPS. Hpx is a glycoprotein with anti- inflammatory effects due, in part, to scavenging of heme, a hemoglobin precursor located in red blood cells (RBCs). Liberation of heme from damaged RBCs has previously been associated with stress exposure, and cell- free heme has deleterious effects including production of reactive oxygen species and promotion of inflammation and pain. AIM 1 will examine the relationship between chronic stress exposure, cell-free heme concentration, and development of pelvic/bladder hypersensitivity in the context of Hpx depletion. AIM 2 will assess whether chronic stress exposure alters nociceptive processing in spinal dorsal horn neurons in Hpx KO and WT mice. AIM 3 will use small animal fMRI to compare brain activity before and after stress exposure in Hpx KO and WT animals. Identification of a mechanistic role of Hpx and/or regulation of heme homeostasis in pain associated with UCPPS will reveal a novel avenue for the therapeutic development. The proposed research will be completed under the mentorship of Dr. DeBerry (Sponsor) and Dr. Bolding (Co-sponsor) and is one component of the fellowship training plan that will enhance the applicant’s expertise in 1) biostatistics, 2) neuroimaging analysis, 3) neuroimmunology in chronic pain, and 4) scientific writing and leadership skills. The proposed research and training will be carried out at the University of Alabama at Birmingham (UAB) Heersink School of Medicine with support from the UAB Graduate School, Behavioral Neuroscience (BN) Doctoral Program, and UAB Small Animal Imaging Shared Facility.
