The objective imperative: advancing chronic orofacial pain research with the brain-heart axis

Takahiko Nagamine

Exploration of Medicine ›› 2026, Vol. 7 ›› Issue (1) : 1001395

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Exploration of Medicine ›› 2026, Vol. 7 ›› Issue (1) :1001395 DOI: 10.37349/emed.2026.1001395
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The objective imperative: advancing chronic orofacial pain research with the brain-heart axis
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Abstract

The biopsychosocial model is the prevailing framework for chronic orofacial pain (COP). While COP is a heterogeneous clinical entity involving nociceptive and neuropathic components, it is increasingly defined by its nociplastic features-a systemic, non-nociceptive state in which psychological factors significantly influence symptoms. Current research frequently suffers from the conflation of constructs. Psychosocial predictors (e.g., self-efficacy) and outcome measures (e.g., pain interference) are often conceptually inseparable. To advance beyond this, we advocate for the integration of the brain-heart axis (BHA). The BHA provides objective, quantifiable markers of autonomic nervous system (ANS) dysregulation, the physical manifestation of chronic stress rooted in large-scale brain network imbalance. The present study proposes a theoretical framework in which psychological distress is reflected in corrected QT interval (QTc) changes, while low self-efficacy is mirrored by reduced heart rate variability (HRV). This integration is supported by the neurochemical roles of N-methyl-D-aspartate (NMDA) receptors in central sensitization and dopamine D2 receptor dysfunction in the basal ganglia. The present paper delineates a framework for research and clinical implementation within advanced dental training.

Keywords

chronic orofacial pain (COP) / brain-heart axis (BHA) / heart rate variability (HRV) / autonomic nervous system (ANS) / nociplastic pain / neuroscience / QTc

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Takahiko Nagamine. The objective imperative: advancing chronic orofacial pain research with the brain-heart axis. Exploration of Medicine, 2026, 7 (1) : 1001395 DOI:10.37349/emed.2026.1001395

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