Implications of circadian disruption on intervertebral disc degeneration: The mediating role of sympathetic nervous system

The circadian clock orchestrates a broad spectrum of physiological processes, crucially modulating human biology across an approximate 24-hour cycle. The circadian disturbances precipitated by modern lifestyle contribute to the occurrence of low back pain (LBP), mainly ascribed to intervertebral disc degeneration (IVDD). The intervertebral disc (IVD) exhibits rhythmic physiological behaviors, with fluctuations in osmotic pressure and hydration levels that synchronized with the diurnal cycle of activity and rest. Over recent decades, advanced molecular biology techniques have shed light on the association between circadian molecules and IVD homeostasis. The complex interplay between circadian rhythm disruption and IVDD is becoming increasingly evident, with the sympathetic nervous system (SNS) emerging as a potential mediator. Synchronized with circadian rhythm through suprachiasmatic nucleus, the SNS regulates diverse physiological functions and metabolic processes, profoundly influences the structural and functional integrity of the IVD. This review synthesizes the current understanding of circadian regulation and sympathetic innervation of the IVD, highlighting advancements in the comprehension of their interactions. We elucidate the impact of circadian system on the physiological functions of IVD through the SNS, advocating for the adoption of chronotherapy as a brand-new and effective strategy to ameliorate IVDD and alleviate LBP.