# Mechanisms of mechanosensation and inflammation-induced hypersensitivityin colon innervating DRG sensory neurons

> **NIH NIH K08** · HARVARD MEDICAL SCHOOL · 2024 · $160,368

## Abstract

Project Summary/Abstract
 Sensation of the gastrointestinal (GI) tract is necessary for physiologic and pathophysiologic processes. During
inflammatory bowel disease (IBD), colonic inflammation induces a hypersensitivity to mechanical stimuli, triggering
abdominal pain. The sensory neurons that innervate the colon and mediate abdominal pain are those with cell bodies within
the dorsal root ganglia (DRG), the DRG sensory neurons. I have recently identified five genetic subtypes of DRG sensory
neurons that innervate the colon and have distinct morphologies and physiologic response properties to distension. I found
that one of these populations, which expresses Bmpr1b, is necessary for inflammation-induced mechanical hypersensitivity.
However, which of the other populations, in particular those that are potential pain-mediating neurons, or nociceptors, are
involved in mediating colonic inflammation-induced mechanical hypersensitivity is unknown. Further, mechanistic details
of how mechanotransduction is mediated in colon innervating DRG neurons remain elusive, as does the mechanism through
which inflammation causes mechanical hypersensitivity. In Aim 1, I propose to use neuronal electrophysiology and mouse
behavior experiments to determine if two other nociceptor populations, which express Sstr2 or Adra2a, are necessary for
colonic inflammation-induced hypersensitivity, to expand our knowledge of the function of colon-innervating nociceptors.
In Aim 2, I will determine differences in localization of the mechanosensory ion channel Piezo2, morphologies, or
ultrastructural properties of colon innervating DRG neurons with distinct mechanical force thresholds, with or without
inflammation, to determine mechanisms of in vivo mechanotransduction. Finally, in Aim 3, I propose to use neuronal
electrophysiology to determine the mechanism through which inflammation causes mechanical hypersensitivity, in
particular through cytokine or prostaglandin signaling. These studies will reveal mechanisms of mechanosensation and
inflammation-induced mechanical hypersensitivity in colon innervating sensory neurons, and perhaps reveal therapeutic
targets to treat abdominal pain in IBD patients.
 I am a physician-scientist applying for a K08 with the long-term goal of becoming a tenure-track, independent
laboratory investigator and academic clinician. I envision developing a research program focused on the mechanisms
through which GI tract innervating sensory neurons respond to diverse stimuli to control physiologic and pathophysiologic
processes. During my proposed K08 research training, I will perform mentored research in the lab of Dr. David Ginty in the
Department of Neurobiology at Harvard Medical School (HMS), a world expert in the field of peripheral neurobiology,
while completing my clinical gastroenterology training at Massachusetts General Hospital (MGH). I have assembled an
expert scientific advisory committee to help guide my K08 research and career development,...

## Key facts

- **NIH application ID:** 11175841
- **Project number:** 7K08DK140638-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Rachel Laura Wolfson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $160,368
- **Award type:** 7
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11175841

## Citation

> US National Institutes of Health, RePORTER application 11175841, Mechanisms of mechanosensation and inflammation-induced hypersensitivityin colon innervating DRG sensory neurons (7K08DK140638-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11175841. Licensed CC0.

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