Chronobiological Mechanisms and Temporal Regulation in Migraine: A Conceptual Review

Background Migraine is a complex neurobiological disorder exhibiting pronounced periodicity, with attack onset frequently clustering at specific circadian times and demonstrating seasonal variation. Traditional Chinese Medicine (TCM) has long recognized the importance of chronological alignment with natural cycles, conceptualizing health as the operational equilibrium between Yin (inhibitory, restorative, nocturnal) and Yang (excitatory, activating, diurnal) forces. This review examines TCM Yin-Yang theory alongside chronobiological findings to explore migraine as a disorder involving dysregulation spanning multiple chronometric scales. Methods A narrative review was conducted applying SANRA guidelines. Literature from PubMed, China National Knowledge Infrastructure, and classical TCM sources was searched for publications related to biological rhythms, migraine, and Yin-Yang theory. The search identified 166 records; 35 articles met the inclusion criteria and were included in this review. Results On a molecular level, circadian clock components (CLOCK/BMAL1, PER/CRY) generate 24-hour rhythms through phased stimulation and repression analogous to Yin-Yang shifts. Limited familial studies report that mutations affecting circadian feedback pathways (e.g., CK1δ) may co-occur with migraine. On an endocrine level, melatonin—a functional correlate of Yin predominance—is reduced in migraineurs, particularly during attacks, and prophylactic melatonin supplementation demonstrates superiority to placebo in preventive studies. On a systemic level, hypothalamic circuits integrate time-related signals governing sleep-wake conversion and autonomic tone; premonitory hypothalamic activation preceding migraine onset reflects dysregulated Yin-Yang balance. . The autonomic nervous system exhibits fluctuations during migraine attacks, with alternating sympathetic (Yang) and parasympathetic (Yin) predominance. Coupled with state-dependent susceptibility to cortical spreading depression, this suggests that migraine reflects a dynamic physiological dysfunction rather than a fixed structural pathology. Conclusion This Yin-Yang rhythmic dysregulation model may inform future investigation of time-based therapeutic strategies targeting circadian realignment, melatonin supplementation, and restoration of autonomic harmony in migraine management.