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.
Status | Active |
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Effective start/end date | 10/1/24 → 9/30/26 |
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