Differential Effects of Pregabalin and Morphine on the Sleep-Wake Cycle and Circadian Rhythms in Mice with Neuropathic Pain

Author: Dai, Wenjing et al.

Anesthesiology. August 2025. doi:10.1097/ALN.0000000000005715

This experimental study investigated the effects of pregabalin and morphine on sleep architecture and circadian rhythms in mice with neuropathic pain induced by spared nerve injury (SNI). Male and female mice were monitored continuously using EEG, EMG, locomotion, and body temperature recordings. After baseline assessment and SNI surgery, mice were treated with either pregabalin (11 mg/kg/day) or morphine (6 mg/kg/day) for 14 days.

SNI disrupted circadian rhythmicity by reducing REM sleep during the habitual sleep phase, increasing wakefulness in females, and impairing locomotor and body temperature rhythms. Pregabalin significantly restored REM sleep, circadian locomotor activity, body temperature rhythmicity, and normalized altered spinal circadian gene expression. It also increased sleep spindle occurrence and strengthened REM sleep power spectra in the 3.5–5.5 Hz range. In contrast, morphine failed to restore REM sleep or circadian rhythmicity and showed only mixed effects on circadian gene expression.

What you should know:

  • Neuropathic pain from SNI disrupts REM sleep, circadian locomotion, and body temperature regulation.

  • Pregabalin, not morphine, restored REM sleep and circadian rhythmicity in mice.

  • Pregabalin also reversed spinal circadian gene expression changes linked to neuropathic pain.

  • Morphine did not improve sleep or circadian function, highlighting a key difference in drug effects.

Thank you to Anesthesiology for allowing me to use and summarize this article.

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