Authors: Dai, Wenjing et al.
Anesthesiology, August 13, 2025. DOI: 10.1097/ALN.0000000000005715
This preclinical study explored how neuropathic pain and two common analgesics—pregabalin and morphine—affect sleep architecture and circadian rhythms. Neuropathic pain often leads to fragmented sleep, altered thermoregulation, and disrupted biological rhythms, but the comparative effects of these treatments on these physiologic systems are poorly characterized.
Male and female C57BL/6JRJ mice were implanted with wireless transmitters for continuous electroencephalographic (EEG), electromyographic (EMG), temperature, and locomotion monitoring. After baseline recordings, researchers induced neuropathic pain via spared nerve injury (SNI) and evaluated behavior and physiology at multiple time points. Following injury, male mice received continuous intraperitoneal infusions of either pregabalin (11 mg/kg/day) or morphine (6 mg/kg/day).
SNI markedly reduced rapid eye movement (REM) sleep, increased wakefulness (especially in females), and disrupted circadian rhythmicity of both locomotor activity and body temperature. Pregabalin, but not morphine, effectively reversed these disturbances—restoring REM sleep duration, stabilizing daily activity and temperature cycles, and normalizing spinal cord circadian gene expression. Pregabalin also increased sleep spindle activity and enhanced low-frequency EEG power during REM sleep, features associated with improved sleep stability and restorative function. Morphine, in contrast, produced minimal improvements and in some cases further disrupted rhythmicity.
These findings demonstrate that neuropathic pain impairs sleep–wake regulation and circadian homeostasis and that pregabalin, unlike morphine, can restore both physiologic and molecular markers of circadian balance.
What You Should Know:
Neuropathic pain disrupts REM sleep and circadian rhythms through changes in spinal and central signaling pathways. Pregabalin, but not morphine, reverses these alterations—highlighting a unique therapeutic role for pregabalin in treating pain-associated sleep and rhythm disorders.
Thank you to Anesthesiology for publishing this important study advancing understanding of how neuropathic pain and its treatments influence sleep and circadian physiology.