Intrinsic Circadian Organization of the Spinal Cord and Dorsal Root Ganglia

Abstract

Circadian rhythms coordinate daily fluctuations in physiology and behavior, yet their organization within primary sensory pathways remains poorly defined. Although somatosensory responsiveness varies across the day-night cycle, it is unclear whether peripheral sensory circuits possess molecular mechanisms for temporal regulation. Here, we demonstrate that the spinal-peripheral sensory axis harbors robust, tissue-autonomous circadian clocks. Using real-time bioluminescence imaging, we observed sustained oscillations of the core clock protein PER2 in the spinal dorsal horn and dorsal root ganglia (DRGs), indicating autonomous circadian timing within these tissues. To define the molecular scope of this regulation, we performed RNA sequencing across a 52-hour circadian time course in DRGs. Circadian analysis identified 626 rhythmic transcripts, representing 3.6% of expressed genes. These genes exhibited non-uniform phase distributions and segregated into discrete temporal clusters. Functional annotation revealed phase-specific enrichment of biological processes related to transport, neuronal structure, and proteostasis, suggesting coordinated temporal deployment of distinct molecular programs rather than uniform oscillations across the circadian cycle. Cross-referencing circadian genes with neuropathic pain-associated gene sets revealed limited overlap; however, overlapping genes aligned to specific baseline phase windows enriched for regenerative annotations. Potassium channel-related signaling components implicated in neuropathic pain also showed baseline circadian modulation. Together, these findings establish the spinal dorsal horn and DRGs as intrinsically circadian tissues and reveal a temporally structured molecular landscape in primary sensory neurons, providing a framework for understanding how peripheral sensory processing, plasticity, and homeostatic regulation are coordinated across the day-night cycle.