# The cellular and molecular mechanisms underlying nociception and pain

> **NIH NIH DP2** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $1,458,000

## Abstract

PROJECT SUMMARY
The perception of pain is caused by intense or damaging noxious stimuli, such as extremes in temperature
or force. The ability to detect noxious stimuli is fundamental for survival as it provides a salient reminder to
animals of imminent or persistent danger. There have been significant efforts in understanding how the
brain generates the perception of pain. Notably, our most efficacious pharmacological treatment for pain
target opiate receptors, which are notorious for their potential for abuse and act primarily on neural circuits
in the brain. Strikingly, there is a comparatively little known about how noxious stimuli are detected initially
by primary sensory neurons known as nociceptors. Nociceptors act as the “first-responders” by detecting
noxious stimuli through axonal projections present in peripheral organs, such as the skin. This information
is then relayed to the brain via synaptic connections made with spinal cord neurons. In order to develop
new pain therapeutics, there is a fundamental need to advance our cellular and molecular understanding of
the peripheral nociceptors. In a recently published study, I performed scRNA-seq on hundreds of thousand
sensory neurons, which identified multiple previously unknown and highly distinct subtypes of nociceptor
neurons, likely with distinct functional roles. In this proposal, the laboratory will focus on implementing our
recently developed molecular genetic tools and approaches to fundamentally advance our understanding
of the first step in pain-processing. We will highlight a three-tiered plan, in which I will thoroughly examine
(Tier 1) the anatomical/biophysical features of nociceptor subtypes, (Tier 2) the molecular mechanisms
underlying noxious stimuli detection by nociceptor subtypes and (Tier 3) the behavioral consequences
during activating/silencing of each nociceptor subtype. we aim to take advantage of my extensive prior
research experience, as well as key preliminary advances, to develop a molecular and cellular
understanding of how nociceptors detect noxious stimuli.

## Key facts

- **NIH application ID:** 10244206
- **Project number:** 1DP2NS127278-01
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Nikhil Sharma
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,458,000
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244206

## Citation

> US National Institutes of Health, RePORTER application 10244206, The cellular and molecular mechanisms underlying nociception and pain (1DP2NS127278-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10244206. Licensed CC0.

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