Elucidating Roles of Distinct Spinal Cord Cell types in Mediating Interstitial Cystitis (IC)/Bladder Pain Syndrome (BPS)

Abstract Interstitial cystitis/bladder pain syndromes (IC/BPS) are a debilitating painful condition with unknown etiology. The cells and the circuits in the spinal cord that process non-noxious (bladder function) and noxious (intense bladder pressure or discomfort) sensory information from the bladder is not well established. What specific roles different spinal anatomical substrates play in processing pathological bladder sensations and voiding dysfunction is unclear. In this proposal, we will test how distinct spinal cord cells that are activated by cystitis are necessary for maladaptive micturition and bladder nociception. We will use chemogenetics and optogenetics approaches to determine the precise roles the cystitis activated spinal cord cells play micturition and bladder nociception. Furthermore, we will determine how this information is streamed to the distinct brain regions. Finally, we propose to perform molecular description of genetically classified spinal cell populations using transcriptomics and fluorescent in situ hybridization. These studies will lead to a cellular and functional characterization of cystitis activated spinal cord cells and to a better understanding of how different symptoms of cystitis are regulated in the spinal cord. These efforts will advance our understanding of spinal circuits in cystitis and may enable development of new therapeutic strategies for the treatment of IC/BPS.