# Validation of a novel cortical biomarker signature for pain

> **NIH NIH R33** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $854,352

## Abstract

Summary
Chronic pain is a major health burden associated with immense economic and social costs. Predictive
biomarkers that can identify individuals at risk of developing severe and persistent pain, which is associated with
worse disability and greater reliance on opioids, would promote aggressive, early intervention that could halt the
transition to chronic pain. Our team has uncovered evidence of a unique cortical biomarker signature that predicts
pain susceptibility (severity and duration). The biomarker signature combines resting state sensorimotor peak
alpha frequency (PAF) measured using electroencephalograph (EEG) and corticomotor excitability (CME)
measured using transcranial magnetic stimulation (TMS). This PAF/CME biomarker signature could be capable
of predicting the severity of pain experienced by an individual minutes to months in the future, as well as the
duration of pain (time to recovery). In the R61 phase of the current proposal, we aim to undertake analytical
validation of this biomarker in healthy participants using a standardized model of the transition to sustained
myofascial temporomandibular pain (masseter intramuscular injection of nerve growth factor, n=150). We will
record PAF/CME at multiple time points before and during the development of pain and use online diaries and
in-laboratory assessments of pain, sleep, stress, and other psychosocial variables. Specifically, we will test if the
biomarker signature predicts an individual's pain sensitivity (high- or low-pain sensitive) with at least 75%
accuracy. We will also test whether the biomarker signature predicts pain severity (on a 0-10 scale) and pain
duration (number of days until pain resolves). We will use multiple statistical approaches to optimize and test the
performance of the predictive biomarker. In the R33 phase we then aim to perform initial clinical validation to
determine whether the optimized PAF/CME biomarker signature predicts pain severity and duration in patients
with new onset myofascial temporomandibular disorder (TMD; n=30). We expect our work to result in the delivery
of a candidate biomarker signature ready for advanced prospective clinical validation studies.

## Key facts

- **NIH application ID:** 10709408
- **Project number:** 4R33NS113269-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joyce Teixeira Da Silva
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $854,352
- **Award type:** 4N
- **Project period:** 2019-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10709408

## Citation

> US National Institutes of Health, RePORTER application 10709408, Validation of a novel cortical biomarker signature for pain (4R33NS113269-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10709408. Licensed CC0.

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