The effect of sleep restriction on laser evoked potentials, thermal sensory and pain thresholds and suprathreshold pain in healthy subjects

Highlights

• Randomized blinded study on the effects of sleep restriction on laser evoked potentials (LEP) amplitude, LEP-habituation, pain threshold and suprathreshold pain in healthy subjects.

• Sleep restriction reduced LEP-amplitudes and thenar cold pain thresholds.

• The results suggest that the observed hyperalgesia after sleep restriction might be caused by cognitive or perceptual mechanisms, rather than sensory amplification.

Abstract

Objective

Sleep restriction seems to change our experience of pain and reduce laser evoked potential (LEP) amplitudes. However, although LEP-habituation abnormalities have been described in painful conditions with comorbid sleep impairment, no study has previously measured the effect of sleep restriction on LEP-habituation, pain thresholds, and suprathreshold pain.

Method

Sixteen males and seventeen females (aged 18–31 years) were randomly assigned to either two nights of delayed bedtime and four hours sleep (partial sleep deprivation) or nine hours sleep. The study subjects slept at home, and the sleep was measured with actigraphy both nights and polysomnography the last night. LEP, thermal thresholds and suprathreshold pain ratings were obtained the day before and the day after intervention. The investigator was blinded. ANOVA was used to evaluate the interaction between sleep restriction and day for each pain-related variable.

Results

LEP-amplitude decreased after sleep restriction (interaction p = 0.02) compared to subjects randomized to nine hours sleep. LEP-habituation was similar in both groups. Thenar cold pain threshold decreased after sleep restriction (interaction p = 0.009). Supra-threshold heat pain rating increased temporarily 10 s after stimulus onset after sleep restriction (interaction p = 0.01), while it did not change after nine hours sleep.

Conclusion

Sleep restriction reduced the CNS response to pain, while some of the subjective pain measures indicated hyperalgesia.

Significance

Since LEP-amplitude is known to reflect both CNS-pain-specific processing and cognitive attentive processing, our results suggest that hyperalgesia after sleep restriction might partly be caused by a reduction in cortical cognitive or perceptual mechanisms, rather than sensory amplification.

Introduction

Although a nociceptive effect of sleep restriction was demonstrated in an experimental study as early as 1934 (Cooperman et al., 1934), there are still uncertainties about the nature of this relationship (Azevedo et al., 2011, Haack and Mullington, 2005, Kundermann et al., 2008, Kundermann et al., 2004, Onen et al., 2001, Roehrs et al., 2006, Schuh-Hofer et al., 2013, Smith et al., 2007, Smith et al., 2005, Tiede et al., 2010). From previous studies it seems that sleep restriction enhances our subjective experience of pain, including reduced pain thresholds, but reduce the brain’s reaction to pain as demonstrated by laser evoked potential (LEP) amplitudes (Azevedo et al., 2011, Tiede et al., 2010).

However, because these studies have considerable methodological variations, e.g. regarding the type of sleep restriction, it is difficult to explain the neurophysiological mechanism behind this apparently contradictory observation. By extending the LEP- and pain thresholds protocol with paradigms reflecting responses to prolonged pain, i.e. also measuring LEP-habituation and temporal summation of suprathreshold heat pain, we might detect sleep restriction-typical patterns. Such patterns might shed more light on the physiology behind the effects of sleep restriction on pain.

Suprathreshold pain paradigms may reflect temporal summation of pain, and give information about central mechanisms of pain hypersensitivity (Granot et al., 2006). Only a few studies have evaluated the effect of sleep restriction on suprathreshold pain and with varying methods, e.g. to a fixed-intensity laser stimulus (Azevedo et al., 2011, Tiede et al., 2010), as pain score to a cold-pressor conditioning stimulus (Smith et al., 2007), as a heat pain tolerance threshold (Onen et al., 2001) or as a pain score to consecutive pin-pricks for wind-up evaluation (Schuh-Hofer et al., 2013). Generally, results suggest that sleep restriction also might cause suprathreshold hyperalgesia. Since generalized (multi-site) hyperalgesia often suggest central mechanisms of pain hypersensitivity, we used two sites (cephalic and upper extremity) for suprathreshold and for pain threshold determination.

Since habituation is a physiological mechanism that protects individuals from responding to repeated stimuli of moderate magnitude and low significance (Coppola et al., 2013), it is interesting that abnormally decreased LEP-habituation has been described in several painful conditions like migraine (Di Clemente et al., 2013, Valeriani et al., 2003) and fibromyalgia (de Tommaso et al., 2014). Furthermore, as epidemiological studies indicate that there is a causal relationship between insomnia and several painful disorders (Boardman et al., 2006, Canivet et al., 2008, Gupta et al., 2007, Hoogendoorn et al., 2001, Kaila-Kangas et al., 2006, Lyngberg et al., 2005, Odegard et al., 2011, Siivola et al., 2004), it would be interesting to find out whether these two observations are related or not. Specifically, if lack of sleep in healthy individuals result in LEP-habituation abnormalities, it might indicate that sleep loss could be the explanatory mechanism for the observed decreased LEP-habituation in migraine and fibromyalgia. As far as we know, no previous study has investigated the effect of sleep restriction on LEP-amplitude habituation.

As we aimed to compare psychophysical pain thresholds with pain-related CNS-responses, most specifically elicited with laser-induced skin heating, the thermal modality was deemed most suitable. This approach is in line with recent interest in more naturalistic sleep restriction-protocols (Finan et al., 2013). As such, a main aim was to investigate how two nights with sleep restriction affected LEP-amplitude and LEP-habituation. A second major aim was to study how sleep restriction affected thermal pain thresholds and suprathreshold heat pain responses. Thermal detection thresholds were also included as control variables to check for unspecific effects of sleep restriction on the somatosensory system, e.g. related to alertness or attention. Hence, it was also a third general aim to compare several variables, reflecting different aspects of thermal pain and sensory physiology, to explore possible sleep restriction-specific abnormality-patterns.