Background Biomarkers would greatly assist chronic pain management. The present study aimed to undertake analytical validation of a sensorimotor cortical biomarker signature for pain consisting of two measures: sensorimotor peak alpha frequency (PAF) and corticomotor excitability (CME), using a human model of prolonged temporomandibular pain (masseter intramuscular injection of nerve growth factor [NGF]).

Methods 150 participants received an injection of NGF to the right masseter muscle on Days 0 and 2, inducing prolonged pain lasting up to 4 weeks. Electroencephalography (EEG) to assess PAF and transcranial magnetic stimulation (TMS) to assess CME were recorded on Days 0, 2 and 5. We determined the predictive accuracy of the PAF/CME biomarker signature using a nested control-test scheme: machine learning models were run on a training set (n = 100), where PAF and CME were predictors and pain sensitivity was the outcome. The winning classifier was assessed on a test set (n = 50) comparing the predicted pain labels against the true labels.

Results The winning classifier was logistic regression, with an outstanding area under the curve (AUC=1.00). The locked model assessed on the test set had excellent performance (AUC=0.88). Results were reproduced across a range of methodological parameters and inclusion of covariates in the modelling. PAF and CME biomarkers showed good-excellent test-retest reliability.

Conclusions This study provides evidence for a sensorimotor cortical biomarker signature for an episode of prolonged pain. The combination of accuracy, reproducibility, and reliability, suggests the PAF/CME biomarker signature has substantial potential for clinical translation.

The authors have declared no competing interest.

This project was funded by the National Institute of Health (R61 NS113269/NS/NINDS NIH HHS/United States).

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Ethical approval was obtained from the University of New South Wales (HC190206) and the University of Maryland Baltimore (HP-00085371).

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↵* Co-first author

↵** Co-senior author

Data availability statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request

Disclosures: This project was funded by the National Institutes of Health (R61 NS113269/NS/NINDS NIH HHS/United States). The authors have no conflicts to declare.

All data produced in the present study are available upon reasonable request to the authors