# Psychophysical distillation of pure pain by nociceptive-specific heating

> **NIH NIH DP2** · EMORY UNIVERSITY · 2024 · $2,314,276

## Abstract

Project Summary: Experimental pain testing in humans, including both quantitative sensory testing (QST) and
functional magnetic resonance imaging (fMRI), is widely used to make inferences about pain processing
mechanisms, including how processing is disrupted in chronic pain. One age-old problem in delivering pain
experimentally is that nociceptors are generally much less sensitive to various physical stimuli (e.g. heating,
pressure, etc.) than innocuous somatosensory receptors. Therefore, experimental pain is almost always evoked
under non-specific conditions in humans. For QST, this means that true, unbiased nociceptive sensitivity cannot
be measured using psychophysical techniques that have provided insight into other sensory modalities. For
fMRI, this means that the brain activity being measured is not specific to nociception, but is instead blended with
innocuous stimulus-evoked activity. To overcome these challenges, we developed a method to selectively
stimulate nociceptors by locating fairly large (>2.56 cm2) naturally occurring areas of skin that are completely
devoid of innocuous warm fibers. By applying noxious heat to these warmth-insensitive regions, we are able to
obtain 1) unbiased measures of nociceptive sensitivity and 2) pure, nociceptive-evoked brain activations. In
addition, we have developed computerized visual analogue scales (VAS) that allow us to assess moment-to-
moment changes in perceived pain, including painful aftersensations, which can then be used to improve
registration of fMRI volumes to patients’ actual experience of pain in the scanner. To further develop and test
the utility of these methods as novel pain biomarkers, this project will enroll both pain-free individuals and those
with fibromyalgia, a nociplastic pain condition. We hypothesize that at least a subset of patients will display
increased unbiased sensitivity to some aspect of nociception, indicating a measurable bottom-up sensitization.
We will then measure the brain’s response to this nociceptive-specific stimulus using fMRI, and compare with
brain activity from stimulation of nearby areas with normal warmth sensitivity. Continuous visual analogue scale
(VAS) ratings of pain of these noxious heat stimuli will help us model each individual’s pain experience and
properly account for the painful aftersensations experienced by many fibromyalgia patients. Instruments and
software programs used in this study will be made readily available to the pain community for use in future
research. Success in this project could also lead to development of a new clinical device for assessing
nociception and pain in isolation.

## Key facts

- **NIH application ID:** 10846260
- **Project number:** 1DP2NS140735-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Daniel Elliott Harper
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,314,276
- **Award type:** 1
- **Project period:** 2024-08-07 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846260

## Citation

> US National Institutes of Health, RePORTER application 10846260, Psychophysical distillation of pure pain by nociceptive-specific heating (1DP2NS140735-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10846260. Licensed CC0.

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