Wearable Nocturnal Autonomic and Sleep Biomarkers for Predicting Next-Day Headache and Identifying Nociplastic Pain in Patients with Migraine

Background/Objectives: The aim of this pilot study was to evaluate the feasibility of developing individualized machine learning models using nocturnal wearable-derived autonomic nervous system (ANS) and sleep metrics to predict next-day headache risk in patients with migraine. We also examined the associations between nocturnal ANS and sleep measures and patient-reported outcome measures (PROMs) related to nociplastic pain, migraine burden, and non-restorative sleep (NRS). Methods: Adults with migraine wore the wrist-worn Empatica EmbracePlus® wearable during sleep and completed daily headache diaries for approximately 4 weeks (N = 10). Participants also completed daily headache diaries and PROMs assessing nociplastic pain, migraine burden, and non-restorative sleep. Personalized machine learning (ML) models were developed to predict next-day headache using nocturnal ANS activity (e.g., pulse rate variability (PRV), electrodermal activity (EDA), respiratory rate (RR)) and sleep metrics (e.g., interruptions, duration, awakenings). Model performance was evaluated using area under the receiver operating characteristic and precision–recall curves (AUROC, AUPRC), sensitivity, specificity, accuracy, and precision. Spearman correlations assessed the relationship between wearable-derived metrics and patient-reported outcome measurements of sleep quality (PROMIS-Fatigue, PROMIS-Sleep Disturbance) and a surrogate marker of nociplastic pain (Fibromyalgia (FM) Score). Results: 9 out of 10 participants wore the EmbracePlus device for at least the target duration of four weeks. For the next-day headache prediction, model performance varied between individuals; area under the ROC curve (AUROC) ranged from 28.2% to 81.2%. Nocturnal measures of EDA were strongly correlated with the FM score (Spearman’s rho = 0.72–0.75, p < 0.05). Conclusions: Phasic EDA may warrant further investigation as a potential physiological indicator related to nociplastic pain mechanisms and next-day headache. However, these findings are preliminary, and larger multicenter trials are needed to confirm results of this pilot study.