# Understanding the spinal circuitry of cold

> **NIH NIH F32** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $64,310

## Abstract

Cutaneous thermosensation is critical for detecting and avoiding potentially harmful environmental temperatures,
as well as thermoregulation. This mechanism frequently goes awry under neuropathic pain conditions,
manifesting as cold hypersensitivity, a condition in which normally cool input is perceived as painfully cold. A
limited understanding of how cold stimuli are encoded in the nervous system has left this debilitating condition
poorly managed. Recent studies suggest that cold input is conveyed from the periphery to the central nervous
system by a population of primary afferents that express the temperature-sensitive cation channel TRPM8.
However, the neural circuits through which this information is processed in the spinal cord and conveyed to the
brain remain almost completely unknown. To address this fundamental gap in knowledge, this proposal will
dissect the neural circuitry that encodes cold stimuli through a combination of behavioral, electrophysiological
and morphological approaches. Based on our preliminary studies, we believe that cold input is conveyed from
the spinal cord to the brain by a subset of neurokinin 1 receptor (NK1R)-expressing spinoparabrachial projection
neurons. To investigate this possibility, our lab recently generated a NK1R-CreER allele, thereby providing us
with genetic access to label and manipulate the activity of NK1R neurons. This proposal will test the hypothesis
that cold input is conveyed from the spinal cord to the brain by a subset of morphologically distinct NK1R neurons
that receive synaptic input (direct or indirect) from cold-sensing, TRPM8 primary sensory afferents. Aim 1 will
investigate whether NK1R spinal projection neurons are required for aversion to cold using behavioral assays.
Aim 2 will dissect the circuitry between TRPM8 primary afferents and NK1R spinal projection neurons that
respond to cold stimuli using electrophysiology and optogenetic approaches in combination with our ex vivo
somatosensory preparation. Aim 3 will determine the morphology of cold-selective spinal projection neurons by
using histology to reconstruct cell architecture within the spinal cord dorsal horn. These experiments will establish
the basic spinal circuitry that mediates cold input, thereby providing a framework from which to investigate
changes in circuitry that underlie cold hypersensitivity in future studies. The success of this multifaceted
fellowship training plan, which includes activities for scientific and career development, will be aided by the
scientific expertise, collaboration, and educational opportunities offered by the Pittsburgh Center for Pain
Research.

## Key facts

- **NIH application ID:** 9847791
- **Project number:** 5F32NS110155-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Tayler Sheahan
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,310
- **Award type:** 5
- **Project period:** 2018-12-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9847791

## Citation

> US National Institutes of Health, RePORTER application 9847791, Understanding the spinal circuitry of cold (5F32NS110155-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9847791. Licensed CC0.

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