Probing Mechanisms of Epithelial-Sensory Nerve Fiber Signaling in Gut Pain.

Abdominal pain, discomfort, and cramping are symptoms commonly experienced by individuals who suffer from inflammatory bowel disease or inflammatory bowel syndrome. Our conscious perception of gastrointestinal pain begins when sensory nerve fibers in the gut are activated or sensitized by chemical agents that we ingest, or that are produced by inflammation, stress, or bacteria. While some of these noxious chemicals interact with sensory nerve fibers directly, others first activate specialized cells, called enterochromaffin (EC) cells, that reside within the gut lining and communicate with sensory nerve endings to transmit pain signals to the brain. We are interested in learning more about the properties of EC cells, how they communicate with sensory nerve endings in the gut, and how this interaction initiates or exacerbates abdominal pain and/or cramping in the setting of inflammation or other insults to the gastrointestinal tract. We also want to know if this communication is bidirectional – that is, do nerve fibers ‘talk back’ to EC cells to regulate their activity or lifetime within the gut? By answering these and related questions, we hope to discover key molecules and mechanisms that contribute to gastrointestinal pain and may therefore represent novel targets for drugs intervention.