Pain reports · 2026
Intrinsic circadian organization of the spinal cord and dorsal root ganglia.
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Yamazaki Shintaro, Wulund Lee, Valekunja Utham K, Reddy Akhilesh B
Аннотация
INTRODUCTION: 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.
OBJECTIVES: To determine whether the spinal-peripheral sensory axis harbors intrinsic circadian clocks and to define the molecular scope and functional organization of circadian regulation in dorsal root ganglia (DRGs).
METHODS: We used real-time bioluminescence imaging to assess circadian oscillations of the core clock protein PER2 in the spinal dorsal horn and DRGs. To characterize molecular regulation, we performed RNA sequencing across a 52-hour circadian time course in DRGs.
RESULTS: We demonstrate that the spinal dorsal horn and DRGs harbor robust, tissue-autonomous circadian clocks, with sustained PER2 oscillations. Circadian analysis identified 626 rhythmic genes (3.6% of expressed genes) in DRGs, with nonuniform phase distributions forming discrete temporal clusters. Functional annotation revealed phase-specific enrichment of processes including transport, neuronal structure, and proteostasis, suggesting coordinated temporal deployment of distinct molecular programs rather than uniform oscillations. Cross-referencing with neuropathic pain-associated genes 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.
CONCLUSION: These findings establish the spinal dorsal horn and DRGs as intrinsically circadian tissues and reveal a temporally structured molecular landscape in DRG, providing a framework for understanding how peripheral sensory processing, plasticity, and homeostatic regulation are coordinated across the day-night cycle.
OBJECTIVES: To determine whether the spinal-peripheral sensory axis harbors intrinsic circadian clocks and to define the molecular scope and functional organization of circadian regulation in dorsal root ganglia (DRGs).
METHODS: We used real-time bioluminescence imaging to assess circadian oscillations of the core clock protein PER2 in the spinal dorsal horn and DRGs. To characterize molecular regulation, we performed RNA sequencing across a 52-hour circadian time course in DRGs.
RESULTS: We demonstrate that the spinal dorsal horn and DRGs harbor robust, tissue-autonomous circadian clocks, with sustained PER2 oscillations. Circadian analysis identified 626 rhythmic genes (3.6% of expressed genes) in DRGs, with nonuniform phase distributions forming discrete temporal clusters. Functional annotation revealed phase-specific enrichment of processes including transport, neuronal structure, and proteostasis, suggesting coordinated temporal deployment of distinct molecular programs rather than uniform oscillations. Cross-referencing with neuropathic pain-associated genes 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.
CONCLUSION: These findings establish the spinal dorsal horn and DRGs as intrinsically circadian tissues and reveal a temporally structured molecular landscape in DRG, providing a framework for understanding how peripheral sensory processing, plasticity, and homeostatic regulation are coordinated across the day-night cycle.