A crossover study evaluating the sex-dependent and sensitizing effects of sleep deprivation using a nociceptive test battery in healthy subjects

Hijma, H.; Koopmans, I.; Klaassen, E.; Doll, R.J.; Zuiker, R.; Groeneveld, G.J.

doi:doi:10.1111/bcp.15505

Aim: We assessed whether total sleep deprivation (TSD) in combination with pain tests yields a reliable method to assess altered pain thresholds, which subsequently may be used to investigate (novel) analgesics in healthy subjects. Methods: This was a two-part randomized crossover study in 24 healthy men and 24 women. Subjects were randomized 1:1 to first complete a day of nonsleep-deprived nociceptive threshold testing, followed directly by a TSD night and morning of sleep-deprived testing, or first complete the TSD night and morning sleep-deprived testing, returning 7 days later for a day of nonsleep-deprived testing. A validated pain test battery (heat, pressure, electrical burst and stair, cold pressor pain test and conditioned pain modulation [CPM] paradigm) and sleep questionnaires were performed. Results: Subjects were significantly sleepier after TSD as measured using sleepiness questionnaires. Cold pressor pain tolerance (PTT, estimate of difference [ED] -10.8%, 95% CI ...Show moreAim: We assessed whether total sleep deprivation (TSD) in combination with pain tests yields a reliable method to assess altered pain thresholds, which subsequently may be used to investigate (novel) analgesics in healthy subjects. Methods: This was a two-part randomized crossover study in 24 healthy men and 24 women. Subjects were randomized 1:1 to first complete a day of nonsleep-deprived nociceptive threshold testing, followed directly by a TSD night and morning of sleep-deprived testing, or first complete the TSD night and morning sleep-deprived testing, returning 7 days later for a day of nonsleep-deprived testing. A validated pain test battery (heat, pressure, electrical burst and stair, cold pressor pain test and conditioned pain modulation [CPM] paradigm) and sleep questionnaires were performed. Results: Subjects were significantly sleepier after TSD as measured using sleepiness questionnaires. Cold pressor pain tolerance (PTT, estimate of difference [ED] -10.8%, 95% CI -17.5 to -3.6%), CPM PTT (ED -0.69 mA, 95% CI -1.36 to -0.03 mA), pressure PTT (ED -11.2%, 95% CI -17.5% to -4.3%) and heat pain detection thresholds (ED -0.74 degrees C, 95% CI -1.34 to -0.14 degrees C) were significantly decreased after TSD compared to the baseline morning assessment in the combined analysis (men + women). Heat hyperalgesia was primarily driven by an effect of TSD in men, whereas cold and pressure hyperalgesia was primarily driven by the effects of TSD observed in women. Conclusions: TSD induced sex-dependent hyperalgesia on cold, heat and pressure pain, and CPM response. These results suggest that the TSD model may be suitable to evaluate (novel) analgesics in early-phase drug studies.Show less

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A crossover study evaluating the sex-dependent and sensitizing effects of sleep deprivation using a nociceptive test battery in healthy subjects