Flavonoid chronotherapy normalizes circadian dynamics and sleep architecture in mice with painful nerve injury

In spared nerve injury PER2::LUC mice, nobiletin (2 mg/kg/day) and tangeretin (1.8 mg/kg/day) restored dorsal root ganglia Per2 rhythm amplitude to pre-surgical levels by post-surgical day 14.

• Why it matters: Painful peripheral nerve injury is linked to disrupted sleep and circadian abnormalities, but it is unclear whether correcting clock dynamics can normalize these disturbances during neuropathic pain.
• What they did: The study used SNI in circadian reporter PER2::LUC mice, tracking real-time Per2 rhythmicity in DRGs and sleep-wake patterns with wireless EEG/EMG, then continuously dosed flavonoids for two weeks via osmotic minipumps.
• The result: Both flavonoids reduced SNI-induced dynamic hypersensitivity on post-surgical day 14, and tangeretin specifically alleviated NREM sleep and wakefulness disturbances, supporting circadian-targeted chronotherapy for neuropathic pain.

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