Influence of Circadian Rhythm on Postoperative Endodontic Pain and Inflammatory Cytokine Expression

Abstract

Postoperative pain remains one of the most common complications following endodontic treatment and is primarily influenced by inflammatory responses within the periapical tissues. Recent evidence suggests that circadian rhythm, the body’s intrinsic biological timing system, plays a significant role in regulating pain perception, immune activity, hormonal secretion, and inflammatory mediator production. Variations in the expression of pro-inflammatory and anti-inflammatory cytokines throughout the day may contribute to differences in the intensity and duration of postoperative endodontic pain among patients. Circadian regulators, including melatonin and clock-related genes, have demonstrated protective effects by modulating oxidative stress, enhancing immune balance, and promoting tissue repair. Understanding these biological mechanisms provides new opportunities for optimizing treatment timing, improving postoperative pain control, and supporting faster healing. Furthermore, advances in digital dentistry and artificial intelligence offer promising approaches for integrating patient-specific biological rhythms with clinical decision-making to develop personalized pain management strategies. This review examines the influence of circadian rhythm on postoperative endodontic pain and inflammatory cytokine expression, highlighting the underlying molecular pathways, clinical implications, and emerging technologies that may enhance therapeutic outcomes. A chronobiology-based approach has the potential to improve patient comfort, reduce inflammatory complications, and contribute to more predictable and individualized endodontic care.