Enteric-sensory neuron circuits that mediate IBD-associated pain

Abdominal pain is the main presenting symptom of patients with Inflammatory Bowel Disease (IBD). However, the neural circuits that mediate gut inflammation-induced abdominal pain remain poorly understood, and thus we lack targeted therapies to treat IBD-associated pain. Sensory neurons connect the gut to the brain to mediate pain responses, but which sensory neurons mediate IBD-associated pain and the mechanisms through which inflammation activates them remain unknown. There are also neurons embedded in the gut wall, termed the enteric nervous system, though their roles in inflammation-induced pain are poorly understood. In previous work, we defined the sensory neuron and enteric neuron subtypes in the gut and found that some sensory neuron subtypes intimately associate with enteric neurons. Here, we propose to define the roles that enteric-sensory neuron communication plays in IBD-associated pain and will further define mechanisms through which inflammatory stimuli alter enteric-sensory communication. This work will have major implications on our understanding of how the peripheral nervous system responds to inflammation during IBD and possibly uncover novel therapeutic targets for IBD-associated abdominal pain, a critical clinical need.