Autonomic pain responses during sleep : a study of heart rate variability

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance.

[1]  J. Trinder,et al.  Autonomic activity during human sleep as a function of time and sleep stage , 2001, Journal of sleep research.

[2]  F. Strian,et al.  Heart rate changes as an autonomic component of the pain response , 1990, Pain.

[3]  M. Soto,et al.  Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis. , 1998, Arthritis and rheumatism.

[4]  V. Legrain,et al.  Laser evoked responses to painful stimulation persist during sleep and predict subsequent arousals , 2008, PAIN®.

[5]  M. Akay,et al.  Short-term analysis of heart-rate variability of adapted wavelet transforms , 1997, IEEE Engineering in Medicine and Biology Magazine.

[6]  M H Bonnet,et al.  The threshold of sleep: perception of sleep as a function of time asleep and auditory threshold. , 1982, Sleep.

[7]  J. Skatrud,et al.  Neurocirculatory consequences of abrupt change in sleep state in humans. , 1996, Journal of applied physiology.

[8]  H. Moldofsky,et al.  Sleep and pain. , 2001, Sleep medicine reviews.

[9]  John Trinder,et al.  Blood pressure and heart rate during continuous experimental sleep fragmentation in healthy adults. , 2008, Sleep.

[10]  J. Trinder,et al.  Cardiac and respiratory activity at arousal from sleep under controlled ventilation conditions. , 2001, Journal of applied physiology.

[11]  V. Ibáñez,et al.  Influence of sleep stage and wakefulness on spectral EEG activity and heart rate variations around periodic leg movements , 2004, Clinical Neurophysiology.

[12]  F. Mauguière,et al.  Human thalamic medial pulvinar nucleus is not activated during paradoxical sleep. , 2004, Cerebral cortex.

[13]  M Steriade,et al.  Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  Valéry Legrain,et al.  Evoked potentials to nociceptive stimuli delivered by CO2 or Nd:YAP lasers , 2008, Clinical Neurophysiology.

[15]  Frédéric Costes,et al.  Wavelet transform of heart rate variability to assess autonomic nervous system activity does not predict arousal from general anesthesia , 2001, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[16]  C. Dubray,et al.  How Pain and Analgesics Disturb Sleep , 2005, The Clinical journal of pain.

[17]  R Lazzara,et al.  Heart rate variability during specific sleep stages. A comparison of healthy subjects with patients after myocardial infarction. , 1995, Circulation.

[18]  M. Bonnet,et al.  Heart rate variability: sleep stage, time of night, and arousal influences. , 1997, Electroencephalography and clinical neurophysiology.

[19]  G. D. Iannetti,et al.  Measurement of skin temperature after infrared laser stimulation , 2006, Neurophysiologie Clinique/Clinical Neurophysiology.

[20]  G. Lavigne,et al.  Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems , 2000, PAIN®.

[21]  M. Boly,et al.  Baseline brain activity fluctuations predict somatosensory perception in humans , 2007, Proceedings of the National Academy of Sciences.

[22]  R. Chervin,et al.  Impaired sleep quality in fibromyalgia: Detection and quantification with ECG-based cardiopulmonary coupling spectrograms. , 2010, Sleep Medicine.

[23]  Anna Blasi,et al.  Cardiovascular variability after arousal from sleep: time-varying spectral analysis. , 2003, Journal of applied physiology.

[24]  D. Goldberg,et al.  A scaled version of the General Health Questionnaire , 1979, Psychological Medicine.

[25]  Q. Aziz,et al.  Exploring relationships for visceral and somatic pain with autonomic control and personality , 2009, PAIN®.

[26]  Jean Claude Barthelemy,et al.  Cardiovascular variability during periodic leg movements: a spectral analysis approach , 2005, Clinical Neurophysiology.

[27]  J. Trinder,et al.  The effects on cardiovascular autonomic control of repetitive arousal from sleep. , 2008, Sleep.

[28]  S Akselrod,et al.  Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability , 1995, Neurology.

[29]  R. Mcevoy,et al.  Noninvasive cardiovascular markers of acoustically induced arousal from non-rapid-eye-movement sleep. , 2002, Sleep.

[30]  V Pichot,et al.  Wavelet transform to quantify heart rate variability and to assess its instantaneous changes. , 1999, Journal of applied physiology.

[31]  S Cerutti,et al.  Power spectral density of heart rate variability as an index of sympatho-vagal interaction in normal and hypertensive subjects. , 1984, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[32]  C. Guilleminault,et al.  EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. , 1992, Sleep.

[33]  Róbert Bódizs,et al.  The nature of arousal in sleep , 2004, Journal of sleep research.

[34]  N. Gosselin,et al.  Age difference in heart rate changes associated with micro-arousals in humans , 2002, Clinical Neurophysiology.

[35]  G. Comi,et al.  IFCN standards for digital recording of clinical EEG. International Federation of Clinical Neurophysiology. , 1998, Electroencephalography and clinical neurophysiology.

[36]  E Ducla-Soares,et al.  Wavelet analysis of autonomic outflow of normal subjects on head‐up tilt, cold pressor test, Valsalva manoeuvre and deep breathing , 2007, Experimental physiology.

[37]  Vincent Ibanez,et al.  Cardiac activation during arousal in humans: further evidence for hierarchy in the arousal response , 2000, Clinical Neurophysiology.

[38]  L. Stegagno,et al.  Heart rate variability during sleep as a function of the sleep cycle , 2003, Biological Psychology.

[39]  G. Lavigne,et al.  Heart rate changes during sleep in response to experimental thermal (nociceptive) stimulations in healthy subjects , 2001, Clinical Neurophysiology.

[40]  E. Sforza,et al.  Time-dependent variation in cerebral and autonomic activity during periodic leg movements in sleep: implications for arousal mechanisms , 2002, Clinical Neurophysiology.

[41]  R. Kakigi,et al.  Pain-related evoked potentials are modulated across the cardiac cycle , 2008, PAIN®.

[42]  A Malliani,et al.  Low-frequency components of cardiovascular variabilities as markers of sympathetic modulation. , 1992, Trends in pharmacological sciences.

[43]  Raffaello Furlan,et al.  Increased Neural Sympathetic Activation in Fibromyalgia Syndrome , 2006, Annals of the New York Academy of Sciences.

[44]  L. Garcia-Larrea,et al.  Inhibition of cortical responses to Aδ inputs by a preceding C-related response: Testing the “first come, first served” hypothesis of cortical laser evoked potentials , 2007, PAIN.

[45]  M. Mahowald,et al.  Sleep fragmentation in rheumatoid arthritis. , 1989, Arthritis and rheumatism.

[46]  S. Quint,et al.  Heart period variability in sleep. , 1995, Electroencephalography and clinical neurophysiology.

[47]  G. Lavigne,et al.  EEG and cardiac activation during periodic leg movements in sleep , 1999, Neurology.

[48]  G. Lavigne,et al.  Experimental pain perception remains equally active over all sleep stages , 2004, Pain.

[49]  J. Paton,et al.  Somatic nociception activates NK1 receptors in the nucleus tractus solitarii to attenuate the baroreceptor cardiac reflex , 2002, The European journal of neuroscience.

[50]  A. Bentley,et al.  Sensitivity of sleep stages to painful thermal stimuli , 2003, Journal of sleep research.

[51]  A. Simonds,et al.  The cardiovascular response to arousal from sleep decreases with age in healthy adults. , 2008, Sleep.