# Nociplastic mechanisms in temporomandibular disorders: Separating nociception from pain

> **NIH NIH R56** · EMORY UNIVERSITY · 2024 · $610,399

## Abstract

Project Summary: Quantitative sensory testing (QST) is widely used to make inferences about pain processing
mechanisms, including how processing is disrupted in chronic pain. However, it is usually not possible to
separate nociceptive from pain sensitivity in these studies. For QST, this means that true, unbiased nociceptive
sensitivity cannot be measured using psychophysical techniques that have provided insight into other sensory
modalities. 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 unbiased measures
of nociceptive sensitivity and compare those with measures of pain sensitivity using the same stimuli (noxious
heat). Nociplastic pain, which is a different mechanistic category from nociceptive and neuropathic, is present in
many chronic pain conditions, including temporomandibular disorders (TMD). However, some patients likely
have more nociplastic mechanisms than others. To extend our knowledge of the mechanisms contributing to
nociplastic pain, this project will enroll both pain-free individuals and those with TMD and employ 1) standardized
QST procedures for assessment of nociplastic pain, multimodal sensory hypersensitivity, and comparison with
other chronic pain conditions like neuropathic pain and fibromyalgia, 2) a novel nociceptive-specific heating
(NoSH) protocol to measure the sensitivity of nociceptors in relation to the perception of pain, and 3) a variety of
endogenous pain-modulatory processes that might contribute to nociceptive and/or pain hypersensitivity in
patients with nociplastic pain. We hypothesize that a subset of TMD patients will display highly probable
nociplastic pain according to the clinical grading criteria. Based on preliminary data, we hypothesize that pain
hypersensitivity is related to suprathreshold mechanisms that modulate nociceptive signals differently in
nociplastic pain. Success in this project could also lead to development of a new clinical biomarker for assessing
nociception and pain in isolation.

## Key facts

- **NIH application ID:** 11137240
- **Project number:** 1R56DE033733-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Daniel Elliott Harper
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $610,399
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11137240

## Citation

> US National Institutes of Health, RePORTER application 11137240, Nociplastic mechanisms in temporomandibular disorders: Separating nociception from pain (1R56DE033733-01). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/11137240. Licensed CC0.

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