ArticlesActivation of the prostaglandin system in response to sleep loss in healthy humans: Potential mediator of increased spontaneous painHaack, Monika*; Lee, Erin; Cohen, Daniel A.; Mullington, Janet M.Author Information Department of Neurology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, USA *Corresponding author. Address: Beth Israel Deaconess Medical Center & Harvard Medical School, East Campus, Dana 779, 330 Brookline Ave., Boston, MA 02215, United States. Tel./fax: +1 617 667 5234. E-mail: [email protected] ARTICLE INFO Article history: Received November 20, 2008; Received in revised form May 19, 2009; Accepted May 29, 2009. Pain: September 2009 - Volume 145 - Issue 1 - p 136-141 doi: 10.1016/j.pain.2009.05.029 Buy Metrics 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 8 h of sleep per night (N = 9), followed by a night of recovery sleep. Participants rated the intensity of various pain-related symptoms every 2 h 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. © 2009 Lippincott Williams & Wilkins, Inc.