Perception of experimental pain is reduced after provoked waking from rapid eye movement sleep

Patients with chronic pain often complain of pain when they wake at night, but the accuracy of their perception of the pain after waking at night is unknown. While cognitive functions are reduced for a short time after waking from sleep, a situation known as sleep inertia, it is unclear how sleep inertia may affect the perception of pain. We investigated the effects of sleep inertia on the perception of experimentally induced pain. Fourteen male volunteers were exposed to a randomized thermal heat stimulus of 43.1 °C ‘hot’ and 46.5 °C ‘hurting’ during provoked waking from Stage 2 sleep, slow wave sleep and rapid eye movement (REM) sleep. Subjects rated their pain on awakening on a Visual Analogue Scale at 30 s after awakening and each minute thereafter for 5 min. We found no change in pain perception over the 5‐min period irrespective of temperature used or sleep stage. However, perceived pain when awoken abruptly from REM sleep was significantly lower than the awake score for both the hot (P = 0.0069) and hurting (P = 0.0025) temperatures. Pain perception when woken from Stage 2 sleep or slow wave sleep was not significantly different from perception when awake. Our findings indicate that sleep inertia reduces pain perception when awoken abruptly from REM. This suggests that patients who wake up in pain either perceive accurately the pain they are experiencing, or at worst underestimate the level of pain if woken from REM sleep.     

EEG arousals in normal sleep: variations induced by total and selective slow-wave sleep deprivation

STUDY OBJECTIVES: Aim of the present study was to assess changes in arousal rates after selective slow-wave (SWS) and total sleep deprivations. DESIGN: Two-way mixed design comparing the arousal index (Al), as expressed by the number of EEG arousals divided by sleep duration, in totally or selectively sleep deprived subjects. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: Nineteen normal male subjects [mean age=23.3 years (S.E.M.=0.55)]. INTERVENTIONS: Al was measured in baseline nights and after selective SWS (N=10) and total sleep deprivation (N=9). MEASUREMENTS AND RESULTS: During the baseline nights AI values changed across sleep stages as follows: stage 1 > stage 2 and REM > SWS, but did not present any significant variations as a function of time elapsed from sleep onset. The recovery after deprivation showed a reduction in EEG arousals, more pronounced after total sleep deprivation; this decrease affected NREM but not REM sleep. During the baseline nights Al showed a close-to-significance negative correlation with REM duration, while during the recovery nights a significant positive relation with stage 1 duration was found. CONCLUSIONS: The present results suggest that recuperative processes after sleep deprivation are also associated with a higher sleep continuity as defined by the reduction of EEG arousals.     

Hypersynchronous delta sleep EEG activity and sudden arousals from slow-wave sleep in adults without a history of parasomnias: clinical and forensic implications

STUDY OBJECTIVES: To determine the frequency of classical markers of non-rapid eye movement (NREM) parasomnias--hypersynchronous delta sleep (HSD) electroencephalogram waves and sudden arousals from slow-wave sleep (SWS)--in patients without histories of somnambulism or other NREM parasomnias. DESIGN: Retrospective review. SETTING: Sleep disorders center laboratory. PATIENTS: 82 consecutive patients without a history of parasomnias who underwent diagnostic polysomnograms; 57 men and 25 women, mean age 48+/-13.3 years, were included without regard to diagnosis or findings. All patients had at least 30 seconds of stage 3 or 4 sleep during the polysomnogram. MEASUREMENTS AND RESULTS: The primary diagnosis of all but 4 patients was obstructive sleep apnea (mean respiratory disturbance index, 30 +/- 23.6 [range, 2.7-117] per hour of sleep). Polysomnograms were then reviewed for the presence of HSD and SWS arousals. A total of 235 arousals (mean, 2.9 +/- 2.7; range, 0-14) from stage 3 or 4 sleep were noted. Eight-five percent of all patients had at least 1 SWS arousal and 45% had 3 or more SWS arousals; 85.1% of all arousals from SWS were secondary to sleep-disordered breathing, and 5.9% were secondary to leg movements. At least 1 episode of HSD (mean, 1.4 +/- 1.6; range, 0-9) was noted in 65.8% of patients. CONCLUSIONS: HSD and SWS arousals were a common finding in patients without clinical histories of sleepwalking or other parasomnias but who were found to have frequent respiratory-related arousals during sleep. HSD and SWS arousals thus have a low specificity for NREM parasomnias and, without further research, are not useful for the objective confirmation of parasomnias in clinical evaluations and in the forensic evaluation of sleepwalking as a legal defense.     

Auditory arousal thresholds of good sleepers and poor sleepers with and without flurazepam.

Auditory arousal thresholds of good (N = 12) and poor (N = 12) sleepers (sleep onset insomniacs) were obtained during stage 2, stage 4, and REM sleep at various times of the night. Despite claims of being "light" sleepers who are easily awakened by noise, poor sleeper auditory arousal thresholds were the same as those of good sleepers. Flurazepam (30 mg) increased the auditory arousal thresholds of poor sleepers (N = 6), but the increase was statistically significant only during the period of peak effect which occurred 1--2 hr after ingestion. Consistent with poor sleeper complaints of trouble falling asleep, the return to sleep (i.e., sleep latency) was significantly longer for poor than for good sleepers following stimulus arousals during the first stage 2 and first stage 4 periods of the night. Sleep latencies for good and poor sleepers did not differ significantly following subsequent arousals. The sleep latency following the first stage 2 stimulus arousal was significantly reduced in poor sleepers during flurazepam-induced sleep.     

Sleep as a tool for evaluating autonomic drive to the heart in cardiac transplant patients

STUDY OBJECTIVES: The aim of this study was to investigate the autonomic drive to the heart in cardiac transplant patients (CTP) using heart rate (HR) and HR variability (HRV) analysis during non-rapid eye movement (NREM)-rapid eye movement (REM) sleep cycles, in particular during arousal associated with the emergence from slow wave sleep (SWS). In healthy subjects, this arousal is characterized by a pronounced HR surge, and HRV is lower during SWS than during the subsequent "active" sleep stage 2 and REM sleep. PARTICIPANTS: The participants were 24 adults, 14 CTP (men, n = 11; women, n = 3; mean age, 62.2 +/- 2.2 years; time after transplantation, 4-14 years) and 10 control subjects (men, n = 7; women, n = 3; mean age, 61.0 +/- 1.8 years). DESIGN: The subjects underwent polygraphic sleep, cardiac, and respiratory recordings during an experimental night. HR was measured during the arousal. HRV was estimated from the R-R intervals in 5-minute stationary segments preceding and following arousal, ie, during SWS and active sleep stage 2 from the first 2 complete NREM-REM sleep cycles. RESULTS: In controls, HR increased during arousal associated with the emergence from SWS during the 2 sleep cycles (P < .05). Sleep-stage-dependent increases of all HRV indexes were observed in the 2 sleep cycles. Concerning CTP, 5 of them displayed a smaller HR increase at arousal, whereas 9 other patients had no HR variation. This distinction between the 2 groups of CTP was confirmed by HRV analysis. The patients with HR reactivity to arousal presented significant sleep-stage-dependent increases in global HRV and sympathetic HRV indexes, whereas the nonreactive group was characterized by an inability of HRV to change with sleep-stage alternation. Sympathetic HRV indexes were significantly higher in the reactive patients than in nonreactive patients, but high frequency power reflecting parasympathetic activity did not differ. However, the absolute HRV indexes were greatly decreased in both groups of patients compared to controls. CONCLUSION: HR reactivity during arousal associated with the emergence from SWS, corroborated by HRV surrounding arousal, may suggest a partial improvement of the sympathetic drive to the heart in some CTP, with no indication of increased parasympathetic activity. Other signs of reinnervation have to be identified to validate this hypothesis.     

Sleep changes vary by odor perception in young adults

Peppermint, a stimulating odor, increases alertness while awake and therefore may inhibit sleep. This study examined peppermint's effects on polysomnographic (PSG) sleep, alertness, and mood when presented before bedtime. Twenty-one healthy sleepers (mean age +/- S.D., 20.1 +/- 2.0 years) completed three consecutive laboratory sessions (adaptation, control, and stimulus nights). Peppermint reduced fatigue and improved mood and was rated as more pleasant, intense, stimulating, and elating than water. These perceptual qualities associated with sleep measures: subjects rating peppermint as very intense had more total sleep than those rating it as moderately intense, and also showed more slow-wave sleep (SWS) in the peppermint than control session. Furthermore, subjects who found peppermint stimulating showed more NREM and less REM sleep while those rating it as sedating took longer to reach SWS. Peppermint did not affect PSG sleep, however, when these perceptual qualities were not considered. Peppermint also produced gender-differentiated responses: it increased NREM sleep in women, but not men, and alertness in men, but not women, compared with the control. Thus, psychological factors, including individual differences in odor perception play an important role in physiological sleep and self-rated mood and alertness changes.     

Relationship of temporal lobe seizures to sleep and arousal: a combined scalp-intracranial electrode study

STUDY OBJECTIVES: The role of arousal from sleep in promoting epileptic seizures is controversial. To examine the question of whether seizures precede or follow arousals from sleep, we defined the timing of temporal lobe seizures in relation to sleep and arousal using combined scalp-intracranial electrodes. DESIGN: Retrospective review of 67 sleep-related mesial temporal lobe seizures in 14 subjects. SETTING: Inpatient epilepsy monitoring laboratory. PATIENTS: Subjects with medically refractory mesial temporal lobe seizures undergoing epilepsy surgery evaluations. INTERVENTIONS: None MEASUREMENTS AND RESULTS: Electroencephalographic (EEG) and/or polygraphic recordings and videotapes were independently reviewed to determine intracranial electrode seizure onset times and time of initial arousal from sleep. In 60 seizures in 13 subjects, intracranial ictal onsets always preceded clinical arousals from sleep. Electrographic signs of arousal in the scalp EEG, defined by the presence of sustained alpha or theta activity, either coincided with or followed, but never preceded, intracranial ictal onsets. In seven seizures in one subject with known seizures upon awakening, intracranial ictal onsets always followed clinical arousals and electrographic signs of arousal from sleep. Seven of the 14 subjects had electrooculogram and chin electromyogram monitoring; in these subjects, no seizures occurred during REM sleep with the majority occurring during NREM stage 2 sleep. CONCLUSIONS: Most sleep-related temporal lobe seizures occurred during NREM sleep and preceded arousals, supporting the premise that processes involved in the initiation and maintenance of NREM sleep play a greater role in facilitating temporal seizures than those involved in promoting REM sleep and arousal. However, arousal from sleep may provoke seizures in exceptional cases.     

Effects of sleep on endotoxin-induced host responses in healthy men

OBJECTIVE: To examine whether increased sleep during viral or bacterial infections supports host defense mechanisms. METHODS: To test this assumption in humans, healthy male subjects were assigned either to sleep from 2300 to 0700 hours (n = 10) or to stay awake through the night (n = 10). In the sleeping subjects Salmonella abortus equi endotoxin (0.4 ng/kg) or placebo were intravenously injected in balanced order during the first SWS episode. The age-matched, sleep-deprived subjects were injected at the same time point. RESULTS: As expected, endotoxin significantly increased rectal temperature, the plasma levels of cortisol, tumor necrosis factor-alpha (TNF-alpha), the soluble TNF receptors p55 and p75, Interleukin (IL)-6, the IL-1 receptor antagonist (RA), leukocyte, and granulocyte counts in both sleeping and sleep-deprived subjects, whereas lymphocyte and monocyte counts were transiently reduced. Time courses of endotoxin-induced host responses did not differ between the sleep and sleep deprivation groups. Endotoxin did not affect the amount of nocturnal wakefulness, nonrapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep across the total night compared with placebo, but significantly increased electroencephalogram-arousals (EEG-arousals) in stage 2 and decreased arousals in SWS. In addition, the amount of SWS, spectral EEG-delta and -theta power was increased at the beginning and at the end of the sleep period, respectively, when the degree of immune activation was relatively low. CONCLUSION: The present results support the notion that short-term sleep deprivation is unlikely to harm the immune system as far as unspecific acute responses are concerned. The effects of endotoxin on sleep in this case support prior observations that in humans, enhanced SWS and intensified NREM sleep occur when host defense activation is subtle.     

The Reliability of Arousal Threshold During Sleep

Thirty-five subjects from two independent studies were awakened at EEG-defined periods during the night with 1000 Hz ascending tone series. Awakenings were made five to eight times per night during stage 2, stage 4, or REM sleep over a series of nights in good and poor sleepers. Reliability was assessed within stage, within night, between stages, and between nights. Good and poor sleepers did not differ in either depth of sleep or reliability of arousal threshold and were thus pooled in the analyses. From night to night, the most consistency was seen in stage 4 (r=.74), although REM reliability (r?₁= .49) and stage 2 reliability (r?₁= .50 and r?₁= .69 in the two respective studies) estimates were also greater than zero. Early sleep onset and morning arousals were more variable. Reliability estimates on arousal thresholds taken within the same night for stage 2 were r= .64 and r?₁= .77 for the two studies and r= .96 for REM. The depth of sleep was not correlated with awake auditory threshold. It was concluded that five or six carefully placed arousals could give a good estimate of an individual's usual arousal threshold.     

Cortical responses to noxious stimuli during sleep

We used magnetoencephalography to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intra-epidermal electrical stimulation, which selectively activates A-delta fibers, was applied to the dorsum of the left hand. While awake, subjects were asked to count the number of stimuli silently (Attention) or ignore the stimuli (Control). During sleep, magnetic fields recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at a latency around 140-160 ms was identified in the awake condition. Multiple source analysis indicated that this main component was generated by activities in the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and cingulate cortex were activated later than the main component. Cortical responses in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate cortex were significantly enhanced in Attention as compared with Control. The main component 1 M as well as later magnetic fields were markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.     

Sleep stage 2: an electroencephalographic, autonomic, and hormonal duality

STUDY OBJECTIVES: It is generally thought that the electroencephalogram of sleep stage 2 is not uniform, depending on whether sleep stage 2 evolves toward slow-wave sleep (SWS) or toward rapid eye movement (REM) sleep. We provide here further evidence of the duality of sleep stage 2 on the basis of its autonomic and hormonal background. PARTICIPANTS: Fourteen healthy men (aged 21-29 years) underwent 1 experimental night. INTERVENTIONS: Sleep and cardiac recordings were taken from 11:00 PM to 7:00 AM. Blood was sampled continuously over 10-minute periods. MEASUREMENTS AND RESULTS: Autonomic activity, as inferred from heart rate variability analysis and hormone profiles, were examined with regard to the normalized hypnograms. We found a dual activity of the autonomic nervous system during sleep stage 2, with a progressive decrease in heart rate variability sympathetic indexes during the transition toward SWS contrasting with high and rather stable levels during sleep stage 2 that evolve toward REM sleep. Also, different profiles were observed in 2 major hormone systems, the activating adrenocorticotropic system and the renin-angiotensin system. Cortisol, in its active period of circadian secretion, was stable during sleep stage 2 preceding SWS and increased significantly when sleep stage 2 preceded REM sleep. For plasma renin activity, sleep stage 2 played a transitional role, initiating increasing levels that peaked during SWS and decreasing levels that reached a nadir during REM sleep. CONCLUSIONS: These results indicate an autonomic and hormonal duality of sleep stage 2 that is characterized by a "quiet" period preparing SWS and an "active" period preceding REM sleep. These differences may confer a fundamental role on this sleep stage in ultradian sleep regulation.     

Sleep architecture changes during a trek from 1400 to 5000 m in the Nepal Himalaya

The aim of this study was to examine sleep architecture at high altitude and its relationship to periodic breathing during incremental increases in altitude. Nineteen normal, sea level-dwelling volunteers were studied at sea level and five altitudes in the Nepal Himalaya. Morning arterial blood gases and overnight polysomnography were performed in 14 subjects at altitudes: 0, 1400, 3500, 3900, 4200 and 5000 m above sea level. Subjects became progressively more hypoxic, hypocapnic and alkalinic with increasing altitude. As expected, sleep architecture was affected by increasing altitude. While time spent in Stage 1 non-rapid eye movement sleep increased at 3500 m and higher ( P  <   0.001), time spent in slow-wave sleep (SWS) decreased as altitude increased. Time spent in rapid eye movement (REM) sleep was well preserved. In subjects who developed periodic breathing during sleep at one or more altitudes (16 of 19), arousals because of periodic breathing predominated, contributing to an increase in the total arousal index. However, there were no differences in sleep architecture or sleeping oxyhaemoglobin saturation between subjects who developed periodic breathing and those who did not. As altitude increased, sleep architecture became progressively more disturbed, with Stage 1 and SWS being affected from 3500 m, while REM sleep was well preserved. Periodic breathing was commonplace at all altitudes, and while associated with increases in arousal indices, did not have any apparent effect on sleep architecture.     

Cognitive Activity, Sleep Disturbance, and Stage Specific Differences Between Recorded and Reported Sleep

Sleepers were studied in their homes to obtain measures of relationships between (a) discrepancies between reported and recorded sleep, (b) degree of sleep difficulty, and (e) reported cognitive activity. Twelve good sleepers and 12 insomniacs were questioned immediately after lights out, at the occurrence of the first sleep spindle or K-complex, 10 min after the second sleep onset, 5 min after the onset of the first REM period, 10 min after the onset of the first stage 2, during subsequent periods of REM and stage 2 sleep, and at spontaneous arousals. Subjects responded to questions regarding mental content (thought vs picture, awake vs asleep, audience vs actor), estimated total time, and estimated total sleep time since the previous arousal. Insomniacs overestimated sleep difficulty only at 10 min after the second spindle and at spontaneous arousals. Reports of “picture” and “actor” were associated with sleeping difficulty. Persons who reported being “awake,”“actor,” and “picture” showed significantly greater discrepancies between reported and recorded sleep than persons who reported “sleep,”“audience,” or “thought”. The results are discussed in terms of implications for increased understanding of the phenomenon of insomnia.     

Analysis of postarousal EEG activity during somnambulistic episodes

Early studies found that electroencephalographic (EEG) recordings during somnambulistic episodes were characterized by a combination of alpha, theta, and delta frequencies, without evidence of clear wakefulness. Three postarousal EEG patterns associated with slow-wave sleep (SWS) arousals were recently identified in adults with sleepwalking and sleep terrors. The goal of the present study was to evaluate the distribution of these postarousal EEG patterns in 10 somnambulistic patients (three males, seven females, mean age: 25.1, SD: 4.1) evaluated at baseline and following 38 h of sleep deprivation. A total of 44 behavioral arousals were recorded in the laboratory; seven episodes at baseline (five from SWS, two from stage 2 sleep) and 37 episodes during recovery sleep (30 from SWS, seven from stage 2 sleep). There was no significant difference in the distribution of postarousal EEG patterns identified during baseline and recovery sleep. One pattern, comprised of diffuse rhythmic and synchronous delta activity, was preferentially associated with relatively simple behavioral episodes but did not occur during episodes from stage 2 sleep. Overall, delta activity was detected in 48% of the behavioral episodes from SWS and in 22% of those from stage 2. There was no evidence of complete awakening during any of the episodes. The results support the view of somnambulism as a disorder of arousal and suggest that sleepwalkers' atypical arousal reactions can manifest themselves in stage 2 sleep in addition to SWS.     

Experimental elevations of blood pressure induced as an internal stimulus during sleep in man: effects on cortical vigilance and response thresholds in different sleep stages

The hypothesis that raising blood pressure (BP) during human sleep, by intravenous administration of angiotensin II, causes arousals was tested. BP was measured intraarterially during polygraphic sleep recordings. Twenty-seven intrasleep elevations of BP in two young adults over 2 nights were evaluated. The BP increases ranged from 16% to 74% of the preexperimental level for systolic BP and from 28% to 84% for diastolic BP. Eighty-one percent of all BP variations induced arousals, and the number of awakenings during elevated BP was 6.5 times higher than in control conditions. These results confirm the hypothesis that BP elevation is an internal stimulus inducing arousal reactions from sleep. The arousals were equally linked to the three phases of BP variation, i.e., rise, peak, and fall in BP, indicating that BP variation functions as a stimulus unit. Arousal thresholds varied with the different sleep stages. They were lowest in sleep stage 2, slightly higher in REM sleep, and highest in slow-wave sleep, in accordance with the thresholds for neutral external stimuli. The study demonstrates the relevance of BP when considering the physiological parameters of sleep-wake regulation.     

Habituation During Sleeping and Waking

EEG and autonomic habituation were studied during sleep stages 2 and REM. and during awake. Repeated presentations of the same stimulus to the same subjects within sleep stages and when awake permitted evaluation of habituation between tone sets within stag 2, REM, and awake, and from sleep to awake. Forty-six subjects were exposed to 800 Hz. 75 dB, 1- or 2-sec tones, presented in sets of 20 tones. During steep, there was no habituation of the EEC response. Habituation occurred for both FPR and HRR during stage 2, with no evidence of within-stage. between tone set habituation. No significant habituation occurred during REM for HRR or FPR. Evoked skin resistance responses were rare during both stage 2 and RKM. In the awake state, HRR was unresponsive but all other variables showed habituation. Tones presented during the night had no effect on the awake response.     

The effects of sleep inertia on decision-making performance

Sleep inertia, the performance impairment that occurs immediately after awakening, has not been studied previously in relation to decision-making performance. Twelve subjects were monitored in the sleep laboratory for one night and twice awoken by a fire alarm (slow wave sleep, SWS and REM sleep). Decision making was measured over 10 3-min trials using the ‘Fire Chief’ computer task under conditions of baseline, SWS and REM arousal. The most important finding was that sleep inertia reduces decision-making performance for at least 30 min with the greatest impairments (in terms of both performance and subjective ratings) being found within 3 min after abrupt nocturnal awakening. Decision-making performance was as little as 51% of optimum (i.e. baseline) during these first few minutes. However, after 30 min, performance may still be as much as 20% below optimum. The initial effects of sleep inertia during the first 9 min are significantly greater after SWS arousal than after REM arousal, but this difference is not sustained. Decision-making performance after REM arousal showed more variability than after SWS arousal. Subjects reported being significantly sleepier and less clear-headed following both SWS and REM awakenings compared with baseline and this was sustained across the full 30 min. In order to generalize this finding to real-life situations, further research is required on the effects of continuous noise, emotional arousal and physical activity on the severity and duration of sleep inertia.     

Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: changes under nCPAP treatment

Nocturnal arousals are the essential cause of disturbed sleep structure in patients with obstructive sleep apnoea syndrome (OSAS). The aim of this study was to analyse the relationship between sleep stages, respiratory (type-R) and movement (type-M) related EEG arousals. Furthermore, the value of these arousals as a criterion for the efficiency of nCPAP treatment was estimated. We examined 38 male patients aged between 30 and 71 (49.1±20.9 SD) y. All patients suffered from OSAS. The mean respiratory disturbance index (RDI) was 47.3±27.8 per h. Polysomnographic monitoring was carried out on 4 subsequent nights: baseline night, 2 nights of nCPAP titration and nCPAP control night. Sleep was visually scored and EEG arousals were classified into type R and M, depending on whether changes of respiration or movement caused the arousal. The RDI, the R index (type-R/h), the M index (type-M/h) and the R and M indices in different sleep stages were calculated. During the baseline night a deficit of slow wave sleep (SWS) and REM sleep was found. Furthermore there were more type-R than type-M arousals registered (17.4 h^?1[3.6–43.6] vs. 5.9 h^?1[1.6–11.8]) ( P <0.01). They occurred during stages NREM 1, NREM 2 and REM ( P <0.01). An SWS sleep rebound and a reduction of the SWS and REM latencies were already found during the first CPAP night. The R index was reduced during the first CPAP night in all sleep stages ( P <0.01) and remained approximately the same in the following 2 nights (3. CPAP night: 1.1 h^?1[0.3–5.0]). Type M arousals occurred more in stages 1 and 2 ( P <0.01), and remained unchanged under nCPAP. We concluded that differentiation of nocturnal arousals may provide more detailed information regarding the influence of breathing disturbances on sleep. Respiratory related, not movement related, arousals may be a useful additional tool in judging the efficiency of OSAS.     

Chemosensory induced arousals during sleep in premenopausal women

Only a limited number of studies is available addressing chemosensory stimulation during sleep. Recent work indicates that stimulation with a nasal irritant produces an increase in arousal frequency in non-REM sleep, whereas a selective olfactory stimulant does not. The present study focused on arousal reactions in REM sleep. Five young healthy volunteers were investigated during 27 nights. Using air-dilution olfactometry CO(2) was used for nasal irritation and H(2)S was used as a specific olfactory stimulant. Both stimuli were presented at four concentrations, odorless stimuli served as control. Other than in previous studies arousal latency was used as a dependent measure. Even the strongest olfactory stimulus did not produce an increase in arousal frequency in REM sleep whereas for irritation such an increase was clearly present. Latencies of arousal responses to CO(2) shortened with increasing stimulus concentrations. Olfactory stimulation does not lead to arousal reactions. In contrast, trigeminal stimulation produces a concentration-dependent increase in arousal frequency and decrease in arousal latency across all sleep stages. The present data shows for the first time that arousals are not present during REM sleep in response to selective olfactory stimuli. However, such changes are easily evoked by irritants activating the trigeminal nerve.     

The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects

The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers.