Understanding mechanisms and SEX-differences in visceral pain
Active Project Grant Awarded Last action
- Award ID
- R01DK135714
- Recipient
-
The Regents Of The University Of California. San Francisco UEI KMH5K9V7S518
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $4,283,476
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date 67% complete
- Place of performance
- San Francisco, CA 94143, USA
Award details come from USAspending.gov.
Description
- Abstract
- Our current understanding of mechanisms underlying visceral hypersensitivity, such as that associated with irritable bowel syndrome (IBS), remains rudimentary. Importantly, treating this and other functional GUT disorders is limited, with a clear need for alternative treatment options. For the growing population afflicted by IBS, GI hypersensitivity and pain persist long after signs of tissue injury have resolved. Unlike other intestinal disorders, patients with IBS are hypersensitive with a lower pain threshold following colonic rectal distention (CRD) testing. Identifying the molecular and cellular components that mediate both the acute and persistent phases of visceral pain is a critical first step in understanding how environmental and endogenous factors produce long-term changes in the nervous system or associated tissues to engender chronic pain syndromes. In this new multi-PI application, we have taken a team-science approach and a multifaceted strategy designed to maximize the relevance of our pre-clinical basic research discoveries. Enterochromaffin (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. Our group recently established that EC cell-mucosal afferent signaling is a major mediator of visceral pain. We also show that the strength of this signal differs in males versus females. We will leverage our new colitis-free chemogenetic model of visceral hypersensitivity to zero in on the contribution of EC cells to visceral pain and identify molecular mechanisms through which these cells modulate the activity of nearby sensory nerve fibers. We will also ask how estrogen signaling contributes to the strong female bias that is characteristic of human IBS. Our team brings expertise in neurophysiology, pharmacology, visceral tissue anatomy, SEX differences, and hormone signaling in female physiology and an unusually wide-ranging set of innovative approaches to tackle a prevalent GUT-brain disorder.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $856,773 | |
| Amendment | $852,896 | |
| Amendment | $822,501 | |
| Amendment | $875,653 | |
| Original award | $875,653 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| South Australian Health And Medical Research Institute LIMITED | $211,468 |
Quick answers
Who received award R01DK135714?
R01DK135714 was awarded to The Regents Of The University Of California. San Francisco by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 1, 2023.
How much is award R01DK135714 worth?
$4,283,476 has been obligated on R01DK135714.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award