Abstract
Disturbed sleep is known to substantially aggravate both the pain condition and the affective state of pain patients. The neurobiological mechanisms underlying these adverse effects are unknown. Oxytocin (OT), being largely involved in social and emotional behavior, is considered to also play a modulatory role in nociception. We hypothesized a pathophysiological role of OT for the hyperalgesic and anxiogenic effects of sleep loss. An established human model of one night of total sleep deprivation (TSD) was used to test this hypothesis. Twenty young healthy students (n = 10 male and n = 10 female) were investigated in a balanced cross-over design, contrasting TSD with a night of habitual sleep (HS). All females took monophasic oral contraceptives (OC) and were investigated during their ‘pill-free’ phase. Plasma OT concentrations were correlated with (1) pain thresholds, (2) descending pain inhibition, and (3) state-anxiety scores. Compared to the HS condition, the plasma OT concentration was significantly increased in sleep deprived females (p = 0.02) but not males (p = 0.69). TSD resulted in pain hypersensitivity to noxious cold (p = 0.05), noxious heat (p = 0.023), and pricking stimuli (p = 0.013) and significantly increased state-anxiety (p = 0.021). While, independent of sex, lower heat pain thresholds correlated with higher plasma OT (p = 0.036), no such associations were found for cold/mechanical pain. In sleep-deprived females, higher plasma OT showed a mild (but insignificant) association with lower pain inhibition (p = 0.093). We found a positive correlation between anxiety-scores and OT (p = 0.021), which was enhanced when respecting “sex” (p = 0.008) and “sleep” (p = 0.001) in a hierarchical regression analysis. Altogether, our study revealed a complex and partially sex-dependent correlation between plasma OT and TSD-induced changes of experimental pain and anxiety. The minor role of OT for TSD-induced changes of evoked pain, and its major involvement in anxiety, argues against a specific role of OT for linking the adverse effects of TSD on pain sensitivity and anxiety with each other. Future investigations are needed in order to dissect out the effect of OC on the sex-dependent effects of TSD observed in our study.
Highlights
Disturbed sleep belongs to the major complaints of pain patients (Taylor et al, 2007; Finan et al, 2013; Nijs et al, 2018)
The saliva samples were stored at −20◦C until shipping to the Biochemical Laboratory, Trier University, FIGURE 1 | Effect of sleep deprivation on plasma oxytocin and cortisol. (A) We found a significant effect of total sleep deprivation (TSD) on oxytocin levels in females, but not males. (B) Based on the entire study population, TSD just failed to change oxytocin levels (p = 0.057). ∗p < 0.05; data are given as mean ± standard error of the mean (SEM)
We found a significant sex ∗ sleep condition interaction with respect to heat pain threshold (HPT) and logMPT, with females becoming more sensitive to heat (p = 0.036) and males becoming more sensitive to pricking pain (p = 0.040)
Summary
Disturbed sleep belongs to the major complaints of pain patients (Taylor et al, 2007; Finan et al, 2013; Nijs et al, 2018). The anxiogenic effect of sleep deprivation has been shown to be correlated with brain morphology changes in the ventromedial prefrontal cortex and – in women – with reduced gray matter volume in the anterior insula and lateral orbitofrontal cortex (GoldsteinPiekarski et al, 2018) Part of these cortical areas – like the insula and the ventromedial prefrontal cortex – do belong to the affective-motivational dimension of pain processing (Peyron et al, 2000; Apkarian et al, 2011; Mutschler et al, 2012; Kragel et al, 2018) but are target regions of the neurohypophysial hormone oxytocin (OT) (Ross and Young, 2009; Riem et al, 2011).
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