Acute and chronic pains originating from the urinary bladder are common clinical entities affecting more than
50% of females at some time in their lives. In an attempt to understand urinary bladder hypersensitivity in a
translational manner, this ongoing research project has used rodents to define basic neurophysiological
elements of bladder sensation at spinal and supraspinal levels. Using urinary bladder distension (UBD)-evoked
reflexes and spinal/supraspinal neuronal responses as experimental endpoints, clinically-relevant models of
bladder hypersensitivity have been developed. The present application explores the role of corticotropin
releasing factor receptors – type 2 (CRF2R) in this bladder hypersensitivity. Three Specific Aims are
Specific Aim #1: To quantitatively characterize, using molecular and neurochemical measures, CRF2R
expression and agonist peptide content in bladder primary afferent neurons (bPANs) & spinal cord
of rats which had NBI & a second adult insult.
Specific Aim #2: To quantitatively characterize effects of CRF2R agonists and antagonists on individual
bPANs in rats which experienced NBI and a second adult insult.
Specific Aim #3: To quantitatively characterize effects of CRF2R agonists and antagonists on spinal
neuronal responses to UBD in rats which experienced NBI and a second adult insult.
These studies will expand upon preliminary studies and will determine quantitatively the effects of the novel
therapeutic agents, CRF2R-antagonists on primary afferent and spinal dorsal horn neuronal responses to
UBD. Effects of pharmacological manipulations related to pain facilitation will be assessed in animals which
experienced neonatal bladder inflammation and controls.
The proposed studies in rodent model systems will give insight related to bladder pain and will explore
novel therapeutics. An improved understanding of sensory processing related to IC and of urinary bladder
sensory pathways and their modulation by secondary insults will result in an increased translation of basic
science to therapeutics for bladder pain.