IPA: Spinal Targets to Treat Persistent Bladder Pain

  • Zhang, Liping (PI)

Grants and Contracts Details

Description

Abstract: Interstitial cystitis/Bladder pain syndrome (IC/BPS) is a painful condition of unknown etiology. IC/BPS often results in poor quality of life and affects approximately 1.08% and 0.66% in female and male veterans and corresponding to 22134 female veterans and 109183 male veterans, respectively. are affected by IC/BPS. Bladder pain is the characteristic symptom of interstitial cystitis/bladder pain syndrome (IC/BPS) where 90% patients do not show any evidence of underlying bladder infection, pathology, or injury. Our long-term goal is to discover novel therapeutic targets for persistent bladder pain. We plan to accomplish this by identifying novel spinal targets capable of modulating persistent bladder pain using a rodent model that is comparable to non-Hunner type IC/BPS: persistent bladder hyperalgesia (BHA) after repeated activation of intravesical protease-activated receptors-4 (PAR4) receptors with minor or no inflammatory changes in the bladder. Our central hypothesis is spinal proteomic changes mediated by activation of specific macrophage migration inhibitory factor (MIF) or high mobility group box 1 (HMGB1) receptors in the lumbosacral spinal cord mediate persistent bladder hyperalgesia without overt bladder injury. We plan to test our central hypothesis by pursuing the following specific aims: 1. Investigate novel MIF-modulated spinal protein targets associated with persistent BHA. We propose to validate a set of lumbosacral proteins that are associated with persistent BHA and that are also modulated by spinal MIF antagonism. In addition, we will examine the functional roles of these proteins in persistent BHA. 2. Determine spinal protein changes mediated by specific receptors in persistent BHA. We propose to investigate the roles of specific spinal MIF or HMGB1 receptors in mediating persistent BHA. Based on our preliminary data, our working hypothesis is that targets identified by unbiased proteomic analysis will show functional roles and that spinal MIF or HMGB1 receptors mediate persistent BHA and are novel targets to modulate persistent BHA. We will apply our established rodent (mouse) model of persistent bladder pain, biochemical and histological approaches for these preclinical studies. Successful completion of these studies is expected to identify new components of the mechanism and to lead to discover novel spinal targets for therapeutic interventions in bladder pain.
StatusActive
Effective start/end date10/1/249/30/26

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