Abstract

Abstract Introduction A bi-directional relationship between sleep and neuropathic pain is of interest because of its impact on human health. Numerous studies in humans and animals have examined the association between sleep and neuropathic pain. However, animal studies showed inconsistent results compared to human data. Therefore, validation of an animal model for sleep-pain association research is needed. We examined the animal models to identify a best-fit model predicting sleep disturbances with the level of neuropathic pain. Methods Adult male C57BL/6J mice (n=7 per group) were implanted with electrodes for electroencephalogram (EEG) and electromyogram. After two weeks of recovery, we obtained baseline EEG data for 24 hours and evaluated the paw withdrawal threshold, a measure of pain sensitivity, by the von Frey test. Afterward, sciatic nerve crush injury (SCI) and common peroneal nerve ligation (CPL) were conducted to make the two different neuropathic pain models. Post-surgery sleep was recorded continuously for 24 hours, followed by von Frey tests. EEG recording during the light period and von Frey tests were repeated on post-surgery days 5, 10, and 15. Results Both SCI and CPL models showed lower paw withdrawal thresholds after the peripheral nerve injury. NREM sleep duration on post-surgery day 1 was reduced significantly compared to baseline in both SCI and CPL, but only SCI showed decreased REM sleep. There was a significant positive correlation between paw withdrawal threshold and NREM sleep duration in SCI (P< 0.0001) but not CPL. Also, wake alpha and theta EEG powers were correlated with pain threshold. Conclusion We confirmed that both models of neuropathic pain disturbed sleep patterns. Nevertheless, sleep disturbances were reliably predicted by the pain sensitivity in the SCI model. Hence, we suggest SCI as a reliable pain model for studying the mechanism of sleep-pain association. Support (if any)

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