Neural Mechanisms Underlying IC/BPS

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Abstract Interstitial cystitis/bladder pain syndromes (IC/BPS) is a debilitating condition with loss of bladder control and severe bladder pain on bladder filling. Mechanisms underlying IC/BPS are poorly understood. Compelling studies show that the brainstem via direct projection to the spinal cord can directly modulate nociceptive processing and bladder function. In our preliminary studies, we have identified distinct populations of the brainstem neurons that project to the spinal cord. Here we will determine the precise roles of these distinct brainstem neurons in the pathology of IC/BPS. We will determine if IC/BPS leads to maladaptive changes in these distinct populations. We will use optogenetics, anatomical tracing, in vivo calcium imaging, slice electrophysiology and RNA sequencing to determine if IC/BPS leads to functional changes at the cellular and systems level in these circuits. Do these changes drive IC/BPS? Does reversing these maladaptive changes relieve IC/BPS? Together, this work will reveal the specific roles for this neural circuits in IC/BPS. This rich information can have broad implications for potential new direction in designing safer therapeutic drugs in treatment of the IC/BPS.