Interstitial cystitis/bladder pain syndrome is a devastating disease with minimal
therapeutic options. While the disease pathophysiology is poorly understood, urothelial
cells are proposed to play a critical role in the modulation of sensory neurons in
the bladder and contribute to disease pathology. It is challenging to determine the
exact role of these cells in sensory signaling, in part because multiple cell types
in the bladder express the same sensory receptors making it challenging to interpret
pharmacological studies. To overcome this challenge, we have developed a novel murine
model where the urothelial cells express channelrhodopsin-2 (ChR2), a nonselective
cation channel that allows for direct stimulation of urothelial cells with light.
Initial validation indicates optical stimulation of these urothelial cells initiates
the release of adenosine triphosphate (ATP), a nociceptive signaling molecule, like
other types of physiological stimulation of these cells. We hypothesize that activation
of urothelial cells and subsequent release of signaling molecules, including ATP,
modulates sensory neuron activity and influences bladder sensory function. Preliminary
recordings of visceromotor responses (VMR), an indirect measure of bladder nociception,
indicate direct stimulation of urothelial cells increases nociceptive response in
animals with bladder inflammation. Additionally, cystometry recordings demonstrate
that optical stimulation of urothelial cells increases bladder pressure and increases
pelvic nerve activity. Collectively, our data suggest that urothelial cells can influence
bladder sensory nerves and potentially nociception. The data collected aids in furthering
our understanding of urothelial-sensory neuron signaling and is a foundation for further
studies on how communication changes with disease progression.
To read this article in full you will need to make a payment
© 2022 Published by Elsevier Inc.