A multisystem phenotype with the Triad of bodily pain, psychological distress, and sleep disturbance was found to have high risk for developing initial onset of painful temporomandibular disorders (TMDs) in the multicenter Orofacial Pain: Prospective Evaluation and Risk Assessment dataset. In this study, we systemically examined phenotypic characteristics and explored potential pathophysiology in quantitative sensory testing and autonomic nervous system domains in this multisystem Triad phenotype. Secondary analysis was performed on 1199 non-Triad and 154 Triad TMD-free Orofacial Pain: Prospective Evaluation and Risk Assessment enrollees at baseline. Results indicated that before developing TMDs, the Triad phenotype demonstrated both orofacial and systemic signs and symptoms that can only be captured through multisystem assessment. In addition, we found significantly lower resting heart rate variability and higher resting heart rate in the Triad phenotype as compared with the non-Triad group. However, pain sensitivity measured by quantitative sensory testing was not different between groups. These findings highlight the importance of whole-person multisystem assessment at the stage before developing complex pain conditions, such as TMDs, and suggest that, in addition to a "tissue damage monitor," pain should be considered in a broader context, such as a component within a "distress monitoring system" at the whole-person level when multisystem issues copresent. Therefore, the presence or absence of multisystem issues may carry critical information when searching for disease mechanisms and developing mechanism-based intervention and prevention strategies for TMDs and related pain conditions. Cardiovascular autonomic function should be further researched when multisystem issues copresent before developing TMDs.
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