Activation of the prostaglandin system in response to sleep loss in healthy humans: potential mediator of increased spontaneous pain

Abstract

Insufficient duration of sleep is a highly prevalent behavioral pattern in society that has been shown to cause an increase in spontaneous pain and sensitivity to noxious stimuli. Prostaglandins (PGs), in particular PGE2, are key mediators of inflammation and pain, and we investigated whether PGE2 is a potential mediator in sleep-loss-induced changes in nociceptive processing. Twenty-four participants (7 females, age 35.1+/-7.1 years) stayed for 7 days in the Clinical Research Center. After two baseline days, participants were randomly assigned to either 3 days of 88 h of sleep deprivation (TSD, N=15) or 8h of sleep per night (N=9), followed by a night of recovery sleep. Participants rated the intensity of various pain-related symptoms every 2h across waking periods on computerized visual analog scales. PGE2 was measured in 24-h-urine collections during baseline and third sleep deprivation day. Spontaneous pain, including headache, muscle pain, stomach pain, generalized body pain, and physical discomfort significantly increased by 5-14 units on a 100-unit scale during TSD, compared to the sleep condition. Urinary PGE2 metabolite significantly increased by about 30% in TSD over sleep condition. TSD-induced increase in spontaneous pain, in particular headache and muscle pain, was significantly correlated with increase in PGE2 metabolite. Activation of the PGE2 system appears to be a potential mediator of increased spontaneous pain in response to insufficient sleep.

Figure 1

Top left: Urine output in 24h collections at baseline and 3^rd day under conditions of TSD (N=15) or control sleep (N=9). Lower left: Urinary PGE2 metabolite levels/24h urine output at baseline and 3^rd day of TSD (N=15) or control sleep (N=9). Lower right: Change of log-transformed urinary PGE2 metabolite levels/24h urine output from baseline to 3^rd day of TSD or control sleep. For statistical analysis, data were log-transformed due to skewed distribution. Asterisk indicate p<0.05 between groups. B=Baseline, Day 1 to 3=Days of TSD or control sleep, R=Recovery.

Figure 2

Intensity ratings of spontaneous measured every 2 hours throughout the protocol. For statistical analysis, ratings were averaged across days and log-transformed (see figure 3)

Figure 3

Left panel: Intensity ratings of spontaneous pain (averaged across days), headache, and muscle pain significantly increased throughout three nights of TSD (N=15) compared to 8h control sleep (N=8, p<0.05 for interaction effect). B=Baseline, Day 1 to 3 = days of TSD or control sleep, R=Recovery. Right panel: Correlation between change in urinary PGE2 metabolite and pain symptoms from baseline to the 3rd day of TSD. Data are log-transformed due to skewed distribution and presented as differences from baseline. Asterisks indicate p<0.05 between groups. Asterisks in parenthesis indicate trend towards significance (p<0.10) between groups.