Beyond Disease Categories: The Adaptive Hierarchical Domain Network (AHDN) for Precision Phenotyping and Personalized...

Background/Objectives: Chronic orofacial pain disorders are highly heterogeneous and therapeutically challenging. Although current classifications such as the International Classification of Orofacial Pain (ICOP) and the concept of nociplastic pain have improved diagnostic consistency, patients with the same diagnosis may show substantial differences in symptom severity, underlying biology, and treatment response. This suggests that disease classifications may describe clinical phenotypes more effectively than the biological mechanisms sustaining persistent pain. This article proposes the Adaptive Hierarchical Domain Network (AHDN) as a conceptual framework for understanding chronic orofacial pain from a precision medicine perspective. Conceptual Framework: AHDN integrates concepts from systems biology, network neuroscience, predictive processing, biomarker research, and precision medicine. It organizes chronic pain across five hierarchically related but dynamically interacting layers: biological susceptibility, peripheral nociceptive drivers, central adaptive plasticity, behavioral adaptation, and social embedding. The framework is intended to complement, rather than replace, established diagnostic classifications. Implications: The proposed framework suggests that burning mouth syndrome, persistent dentoalveolar pain disorder, persistent idiopathic facial pain, occlusal dysesthesia, and subsets of temporomandibular disorders may represent different mechanistic configurations within a shared adaptive network. AHDN provides a hypothesis-generating structure for mechanistic phenotyping, biomarker development, and individualized management. However, the framework remains conceptual and requires prospective clinical validation, standardized assessment methods, and evaluation of its clinical utility before routine implementation.