# CRCNS: Molecular and Computational Dissection of Cold Nociception

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2021 · $341,068

## Abstract

The long-term goal of this proposal is to understand the molecular and physiological bases of cold
nociception. Thermosensory nociception is a specialized form of somatosensation essential to the survival
of all metazoans. Thermosensory nociception alerts the organism to potential environmental dangers
coupled with pain sensation thereby serving as a protective mechanism for driving adaptive behavioral
responses to safeguard against incipient damage. Despite this importance, the fundamental molecular and
biophysical bases of cold nociception remain poorly understood. Molecularly, transient receptor potential
channels (i.e. thermoTRPs) play critical roles in thermosensation, however, relatively less is known
regarding how thermoTRPs mechanistically function in regulating noxious cold detection. Neurologically,
acute and chronic pain may manifest as altered thermosensory nociception whereby innocuous thermal
stimuli erroneously engage nociceptive circuitry leading to neuropathic pain. Cold hypersensitivity is
associated with multiple sclerosis, fibromyalgia, stroke, and chemotherapy-induced neuropathy resulting in
neuropathic pain, however the mechanisms underlying cold sensitization are largely unknown. Here, we
will investigate a fundamental problem of how multimodal sensory neurons discriminately detect noxious
cold stimuli to elicit nocict9ptive behavior using Drosophila as a model system in combination with bi-
directionally linked neurogenetic, neurogenomic, cellular imaging, electrophysiological, behavioral,
computational modeling, and bifurcation analyses. We aim to uncover molecular and biophysical bases for
cold-evoked nociceptive stimulus coding, including the functional properties of thermoTRPs and Ca2·
signaling dynamics in this process. The project aims and outcomes of this research will significantly
advance our knowledge of cold nociception by addressing three open questions: (1) What are the
molecular and biophysical bases of cold nociceptive stimulus coding? (2) How do multimodal nociceptive
neurons discriminately detect noxious stimuli (e.g. cold) to drive nocifensive behavior? (3) How do
thermoTRPs and Ca2· signaling mechanisms mechanistically function in regulating noxious cold detection?
More generally, the bi-directional integration of experimental and computational approaches in a closed-
loop investigational strategy is well-suited to transform our understanding of cold nociception by elucidating
potentially generalizable mechanisms of cold thermosensory coding, including roles of TRP channels and.
Ca2· homeostasis in sensory-evoked neural activity.
RELEVANCE (See instructions):
The perception of noxious stimuli is often coupled to pain sensation as a protective mechanism, however
altered temperature sensation may lead to neuropathic pain (e.g. in multiple sclerosis, fibromyalgia, and
stroke) where patients experience pain due to cold hypersensitivity. By uncovering basic mechanisms of
noxious cold perception, we develop im...

## Key facts

- **NIH application ID:** 10175071
- **Project number:** 5R01NS115209-03
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** GENNADY S CYMBALYUK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $341,068
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175071

## Citation

> US National Institutes of Health, RePORTER application 10175071, CRCNS: Molecular and Computational Dissection of Cold Nociception (5R01NS115209-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10175071. Licensed CC0.

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