Sleep deprivation and recovery sleep affect healthy male resident's pain sensitivity and oxidative stress markers: The medial prefrontal cortex may play a role in sleep deprivation model

Abstract

Sleep is essential for the body's repair and recovery, including supplementation with antioxidants to maintain the balance of the body's redox state. Changes in sleep patterns have been reported to alter this repair function, leading to changes in disease susceptibility or behavior. Here, we recruited healthy male physicians and measured the extent of the effect of overnight sleep deprivation (SD) and recovery sleep (RS) on nociceptive thresholds and systemic (plasma-derived) redox metabolism, namely, the major antioxidants glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD). Twenty subjects underwent morning measurements before and after overnight total SD and RS. We found that one night of SD can lead to increased nociceptive hypersensitivity and the pain scores of the Numerical Rating Scale (NRS) and that one night of RS can reverse this change. Pre- and post-SD biochemical assays showed an increase in MDA levels and CAT activity and a decrease in GSH levels and SOD activity after overnight SD. Biochemical assays before and after RS showed a partial recovery of MDA levels and a basic recovery of CAT activity to baseline levels. An animal study showed that SD can cause a significant decrease in the paw withdrawal threshold and paw withdrawal latency in rats, and after 4 days of unrestricted sleep, pain thresholds can be restored to normal. We performed proteomics in the rat medial prefrontal cortex (mPFC) and showed that 37 proteins were significantly altered after 6 days of SD. Current findings showed that SD causes nociceptive hyperalgesia and oxidative stress, and RS can restore pain thresholds and repair oxidative stress damage in the body. However, one night of RS is not enough for repairing oxidative stress damage in the human body.

Keywords: night shift; oxidative stress; pain; recovery sleep; sleep deprivation.

FIGURE 1

Study protocols.

FIGURE 2

Epworth sleepiness scale scores. Subjects were scored on the Epworth sleepiness scale at three time points. Sleep deprivation significantly increased subjects’ daytime sleepiness compared to baseline, and this was significantly reduced after recovery sleep. ****P < 0.0001 compared to SD.

FIGURE 3

Pressure pain threshold (A) and NRS subjective pain scores (B). Subjects’ changes in pressure pain threshold and subjective NRS scores. Sleep deprivation (SD) significantly increased perceived pain compared to baseline, and this nociceptive hyperalgesia was significantly reduced after recovery sleep (RS). ^#P < 0.05 compared to SD. **P < 0.01 compared to SD.

FIGURE 4

Paw withdrawal threshold (A) and paw withdrawal latency (B) in rats. Rats 1–8 in the Sham group and 1–8 in the SDR group. The PWT and PWL of rats decreased significantly after 6 days of SD, and the PWL recovered after 2 days of RS compared to 6 days of SD, and both PWT and PWL returned to baseline levels after 4 days of RS. ****P < 0.0001 compared to the sham group. ^####P < 0.0001 compared with baseline and RS4d in the SDR group.

FIGURE 5

Plasma GSH (A), MDA (B), SOD (C), and CAT (D) levels or activity measurements before and after SD and RS. **P < 0.01 compared to Baseline, ****P < 0.0001 compared to Baseline, ^#P < 0.05 compared to SD, ^####P < 0.0001 compared to SD.

FIGURE 6

Volcano diagram: Rats 9–14 in the sham group and 9–13 in the SDR group. Differentially expressed proteins were displayed in the volcano diagram. Y-axis: -log10 (p-value); X-axis: log2 (ratio). The dots that lie beyond the two vertical boundaries and above the horizontal boundaries represent proteins that differ significantly. Clear spots in salient regions mean that these proteins do not meet the other conditions.

FIGURE 7

Gene ontology (GO) cellular components. Top axis is -log10 (p-values) and bottom axis is gene count. The ontology covers three domains: biological process, cellular component, and molecular function.

FIGURE 8

Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed proteins. KEGG pathway annotation was performed on the selected differentially expressed proteins to analyze and determine the most important metabolic and signal transduction pathways involved in the differentially expressed proteins.

FIGURE 9

STRINGdb protein–protein network enrichment analysis. The protein–protein interaction network of significant proteins is shown. STRING database integrates various information from curated databases that were experimentally determined; gene neighborhood, gene fusions, and gene co-occurrence; text mining, co-expression, and protein homology.