SPARC ‐ Mapping Gut‐Spinal Cord Connections in Visceral Pain

Abstract

Our current understanding of mechanisms underlying visceral pain, including that associated with irritable bowel syndrome, remains rudimentary. Importantly, opiates are ineffective at treating visceral pain syndromes, and only exacerbate discomfort by producing constipation, reflecting a clear need for alternative treatment options. Our goal is to bring greater mechanistic insight to this underserved area of pain research, and to approach the problem in a multifaceted strategy designed to maximize the relevance of our basic research discoveries to future pain treatments. Specifically, we are asking how enterochromaffin (EC) cells transmit noxious signals from the gut lumen to the spinal cord. EC cells are key sensory cells in the intestinal epithelium that release serotonin onto primary sensory nerve fibers, thereby evoking a sensation of discomfort and pain in response to luminal irritants, such as bacterial metabolites, inflammatory agents, or ingested chemicals. We are using transgenic moue models to selectively activate and silence EC cells to examine their functional connections with sensory nerve fibers and spinal circuits. We are coupling these tools with transcriptome profiling, viral tracing, and electrophysiological methods to gain insights into the molecular and functional identity of these fibers.Support or Funding InformationNIH R35 NS105038, NIH U01 NS113869, Rainin Foundation, Giannini Foundation