PROJECT SUMMARY/ABSTRACT
Hypersensitivity of the urogenital organs and pelvic region is associated with urologic chronic pelvic pain
syndrome (UCPPS; inclusive of interstitial cystitis/painful bladder syndrome and chronic prostatitis). Evidence
from animal models demonstrates that central nervous system processing of urogenital/pelvic sensory
information may be modified individually by (i) neonatal events that occur during sensory development and that
permanently alter neuroanatomical substrates, or (ii) adverse events, such as stress or trauma, experienced
during development or adulthood. Both of these phenomena have a high degree of clinical relevance, and there
is good reason to believe that consequential alterations in the phenotype and function of primary afferent neurons
innervating the urogenital and pelvic region are critical for the development of hypersensitivity and, thus, would
serve as targets for therapeutic intervention. The long-term goal of this project is to systematically study changes
in primary afferent-to-spinal cord sensory processing of somatic and visceral urogenital structures in clinically
relevant animal models of UCPPS. The objective of the current proposal is to systematically examine the effects
of neonatal bladder inflammation (NBI) or maternal separation (NMS), alone and in combination with an adult
insult of the same class (bladder re-inflammation, acute or chronic stress), on urogenital hypersensitivity and/or
widespread pain. The guiding hypothesis that serves as the basis of this proposal is that experiencing early life
inflammation or stress alters distinct subclasses of urogenital primary afferent and spinal dorsal horn neurons
that, in turn, inhibit or augment urogenital sensitivity in the context of a secondary adult exposure to inflammation
or stress. This hypothesis will be addressed in three specific aims using: 1) in vivo reflex behaviors coupled with
optogenetic targeting of stratified neuronal populations to determine how NBI or NMS alter primary afferent-
driven reflex behaviors, 2) patch-clamp and extracellular in vivo electrophysiology to characterize functional
activity within urogenital afferent and spinal dorsal horn neuronal pathways following NBI or NMS, and 3)
neurochemistry and optogenetics to identify neurochemical mediators and receptors/transducers in urogenital
tissues, primary afferent neurons, and spinal dorsal horn involved in the development of pelvic hypersensitivity.