SLEEP

Lydic, Ralph

doi: 10.1093/sleep/24.1.10pmid: 11204045

Sandrini, Giorgio; Milanov, Ivan; Rossi, Bruno; Murri, Luigi; Alfonsi, Enrico; Moglia, Arrigo; Nappi, Giuseppe

doi: 10.1093/sleep/24.1.13pmid: 11204048

Abstract:Controversy continues to surround the monosynaptic and polysynaptic spinal reflexes during the different stages of sleep. In animal studies both of these reflexes were found to be depressed during desynchronized sleep. In humans, the H reflex was unchanged whereas the second component of the nociceptive flexion reflex was increased. However, abolition of the H reflex and F waves during REM sleep has also been reported.The aim of this investigation was to examine the effects of different sleep stages on the polysynaptic nociceptive flexion reflex.Six healthy volunteers were studied. The RIII reflex was studied according to Willer's method (1977) during the different stages of NREM and REM sleep.The RIII reflex threshold was found to increase during stage 2 of NREM sleep. It remained higher during stages 3 and 4. During REM sleep a further increase in the reflex threshold was observed. The reflex latency was prolonged during stage 4 of NREM sleep. There was evidence of further latency prolongation during REM sleep. It was also during REM sleep that the maximum increase in the amplitude and duration of the reflex were recorded.

Soja, Peter J.; Pang, Walton; Taepavarapruk, Niwat; McErlane, Shelly A.

doi: 10.1093/sleep/24.1.18pmid: 11204049

Abstract:Sleep mentation studies infer that pain sensation in humans may be reduced during active REM sleep. However, to provide a mechanistic explanation for this phenomenon, few, if any neurophysiological studies have been performed at the lumbar level from neurons comprising classical pain pathways during sleep and wakefulness. The spinoreticular tract is one such classical pathway that has been implicated in the rostral transmission of nociceptive information. The present study was performed to determine if the activity of spinoreticular tract (SRT) neurons is dependent upon behavioral state. Accordingly, extracellular recording techniques were used to monitor the activity of identified SRT neurons in unanesthetized chronic cats during sleep and wakefulness. The ongoing spike activity of SRT neurons was found to be relatively uniform when the states of quiet wakefulness and quiet sleep were compared. However, during active sleep, the majority of the SRT neurons sampled underwent a sustained reduction in spike activity. Marked facilitation of SRT cell activity occurred in a few instances. These data provide the first unitary evidence supporting earlier evoked potential, psychophysical and clinical studies that ascending sensory information in a classical pain pathway is regulated in a state-dependent fashion.

Antognini, Joseph F; Saadi, Jeffrey; Wang, Xiao Wei; Carstens, Earl; Piercy, Marla

doi: 10.1093/sleep/24.1.26pmid: 11204050

AbstractStudy Objectives:Anesthetics, including propofol, depress the electroencephalogram (EEG) and neuronal activity in the midbrain reticular formation (MRF). Because propofol has anesthetic effects in the spinal cord, we hypothesized that it would indirectly depress EEG and MRF neuronal responses to noxious stimulation in part by a spinal cord action.Design:Six goats were anesthetized with isoflurane and the jugular veins and carotid arteries were isolated to permit cranial bypass and differential propofol delivery. A noxious mechanical stimulus was applied to the distal forelimb while recording bifrontal EEG and MRF single-unit activities. Propofol was separately administered to the cranial (0.08±0.06 mg/kg) and torso circulations (4 mg/kg) and the noxious stimulus applied at 1,5, 10, and 15 min after each injection.Setting:N/APatients or Participants:N/AInterventions:N/AMeasurements and Results:Noxious stimulation decreased total power (TP) from 96±33µV2/Hz to 38 ± 20µV2/Hz, (mean±SD) and increased spectral edge frequency (SEF) from 10±3 Hz to 19±5 Hz (p<0.01). Propofol administered to the torso prevented stimulus-evoked changes in TP (121± 80µV2/Hz, 121 ± 74µV2/Hz, 114±74µV2/Hz at 1,5, and 10 min respectively, p<0.01 compared to control evoked response) and SEF (11±6Hz, 9±2Hz, 10±6Hz, and 12±5Hz at 1, 5, 10 and 15 min, respectively, p<0.001 compared to control evoked response). Propofol administered to the cranial circulation significantly blunted the EEG and MRF response, while torso-administered propofol had slight effects on MRF responses.Conclusions:Propofol blunted the EEG response to noxious stimulation in part via a subcortical action.

Mason, Peggy; Escobedo, Irma; Burgin, Christina; Bergan, Joe; Lee, Ji Hwan; Last, E.J.; Holub, Allana L.

doi: 10.1093/sleep/24.1.32pmid: 11204051

Abstract:Brainstem neurons that are thought to modulate pain are reported to have state-dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states.Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw—a focused light bulb (“radiant heat”) and a CO2 laser (“laser heat”)—were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping.The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles.

Cronin, Arthur J.; Keifer, John C.; Davies, Matthew F.; King, Tonya S.; Bixler, Edward O.

doi: 10.1093/sleep/24.1.39pmid: 11204052

AbstractStudy Objectives:To test the hypothesis that opioids and pain contribute independently to postoperative sleep disturbance, 10 women undergoing surgery requiring a low abdominal incision for treatment of benign gynecologic conditions were randomized to receive either epidural opioid (fentanyl) (n=6) or epidural local anesthetic (bupivacaine) (n=4) for intraoperative and postoperative analgesia. Design: N/ASetting:N/APatients or Participants:N/AInterventions:N/AMeasurements:Polysomnography was performed in a standard patient room on the preoperative and first three postoperative nights. Pain at rest and with coughing was evaluated using a visual-analogue pain scale each evening and morning.Results:On the first postoperative night, rapid eye movement (REM) sleep was abolished in all patients. On the third postoperative night, the mean±SE REM sleep time increased significantly (p=.003) to 9.8%±3.1% in the fentanyl group, and 12.9%±3.8% in the bupivacaine group. Conversely, light non-REM (NREM) sleep (%stage 1 + %stage 2) was higher on the first postoperative night and significantly lower on the third postoperative night (p=0.011). Between group comparison revealed only that the mean % slow-wave sleep (SWS) in the fentanyl group (6.0%, 2.0%, and 14.7%) was different from the bupivacaine group (7.8%, 9.1%, and 10.6%) in the postoperative period after adjusting for the preoperative night % SWS (p=0.021). Pain was well controlled in all patients, but was slightly better controlled in the fentanyl group than in the bupivacaine group on postoperative night 2 (p=0.024). There was no statistically significant association between pain score and any polysomnographically defined stage.Conclusion:Postoperative patients suffer a profound sleep disturbance even when opioids are avoided and pain is well controlled.

Rose, Mary; Sanford, Art; Thomas, Christopher; Opp, Mark R.

doi: 10.1093/sleep/24.1.45pmid: N/A

Abstract:Although few studies have been conducted on burn patients, they indicate that sleep of burned children is altered. We suggest in this review, on the basis of the limited data available that factors contributing to sleep disruption in burned individuals may be broadly categorized as pathophysiological responses to the injury, the pain and discomfort experienced by the patient and medications used to treat these symptoms, and the physical environment in the Burns Intensive Care Unit. The responses to thermal injury include alterations in circulating neuropeptides, hormones, and immune-active substances, many of which are known to regulate/modulate sleep. Medications for the management of pain and for treating symptoms of various injury-induced stress and anxiety disorders may also alter sleep. Finally, frequent disruptions of the patient by medical staff is but one of the many environmental factors that may contribute to disrupted sleep. Severe burns induce a hypermetabolic response that may result in peripheral wasting, that depletes substrates necessary for tissue repair, and is associated with reduced growth hormone. Burn-induced growth hormone insufficiency is aggressively treated to counteract peripheral wasting and to aid in wound healing of skin graft donor sites. We speculate that improvement of sleep quality would result in a less severe reduction in growth hormone due to the well documented relationship between slow-wave sleep onset and growth hormone secretion. Such improvement in spontaneous growth hormone secretion patterns may aid in recovery by supporting tissue repair and by minimizing the hypermetabolic response to thermal injury. The experiments to test such hypotheses remain to be conducted, yet the results of such experiments may provide the basis for beginning to answer the question of whether or not sleep aids in recovery from injury.

Tanase, Diana; Martin, Wilbur A.; Baghdoyan, Helen A.; Lydic, Ralph

doi: 10.1093/sleep/24.1.52pmid: 11204054

AbstractStudy Objectives:Opioids delivered to the pons inhibit REM sleep, whereas pontine administration of adenosine enhances REM sleep. In other brain areas opioids and adenosine interact to produce antinociception. Adenosine A1 receptors and mu opioid receptors each activate Gi/Go proteins. This study tested the hypothesis that combined treatment with the adenosine A1 receptor agonist SPA and the mu opioid agonist DAMGO would enhance G protein activation to a greater level than produced by either agonist alone. G protein activation was quantified in seven brainstem regions regulating sleep and nociception. This study also tested the hypothesis that G protein activation caused by SPA would be concentration dependent and blocked by the adenosine A1 receptor antagonist DPCPX.Design:Activation of G proteins was assessed autoradiographically by agonist stimulation of [35S]GTPγS binding in slide-mounted sections of rat brainstem. G protein activation was quantified in nCi/g tissue for pontine reticular formation, dorsal raphe, ventrolateral and dorsomedial periaqueductal gray, and laterodorsal and pedunculopontine tegmental nuclei.Setting:N/APatients or Participants:N/AMeasurements and Results:Combined treatment with SPA and DAMGO caused a partially additive increase in G protein activation that was significantly (p<0.01) greater than G protein activation caused by either agonist alone. Treatment with SPA alone caused a concentration dependent (p<0.001) increase in [35S]GTPγS binding that was blocked by DPCPX.Conclusion:Agonist activation of adenosine A1 receptors stimulates G proteins in brainstem nuclei regulating sleep and nociception. In these same nuclei, G protein activation by combined treatment with DAMGO and SPA was partially additive, suggesting that mu opioid and adenosine A1 receptors activate some common G protein pools.

Zhang, Jian-Hua; Sampogna, Sharon; Morales, Francisco R.; Chase, Michael H.

doi: 10.1093/sleep/24.1.67pmid: 11204055

Abstract:Orexin-A-like immunoreactive (OrA-ir) neurons and terminals in the cat hypothalamus were examined using immunohistochemical techniques. OrA-ir neurons were found principally in the lateral hypothalamic area (LHA) at the level of the tuberal cinereum and in the dorsal and posterior hypothalamic areas. In the LHA the majority of the neurons were located dorsal and lateral to the fornix; a small number of OrA-ir neurons were also present in other regions of the hypothalamus. OrA-ir fibers with varicose terminals were detected in almost all hypothalamic regions. The high density of fibers was located in the suprachiasmatic nucleus, the infundibular nucleus (INF), the tuberomamillary nucleus (TM) and the supra- and pre-mamillary nuclei.Ultrastructural analysis revealed that OrA-ir neurons in the LHA receive abundant input from non-immunoreactive terminals. These terminals, which contained many small, clear, round vesicles with a few large, dense core vesicles, made asymmetrical synaptic contacts with OrA-ir dendrites, indicating that the activity of orexin neurons is under excitatory control. On the other hand, the terminals of OrA-ir neurons also made asymmetrical synaptic contact with dendrites in the LHA, the INF and the TM. The dendrites in the LHA were both non-immunoreactive and OrAir; conversely, the dendrites in the INF and the TM were non-immunoreactive. In these regions, OrA-ir terminals contained many small, clear, round vesicles with few large, dense core vesicles, suggesting that orexinergic neurons also provide excitatory input to other neurons in these regions.

Gora, John; Colrain, Ian M.; Trinder, John

doi: 10.1093/sleep/24.1.81pmid: 11204056

AbstractStudy Objectives:To determine whether the cortical response to mid-inspiratory occlusions can be used as a model of the cortical response to obstructive events during sleep; and to determine whether the vertex sharp wave (VSW) and K-complex are exclusive contributors to the N350 and N550 components respectively of the stage 2 sleep event-related potential.Design:Two types of respiratory stimuli were used to elicit evoked potential responses during stage 2 NREM sleep. These were mid-inspiratory occlusions and complete breath obstructions. Trials were grouped according to the type of phasic response elicited; isolated K-complex (KC), VSW associated with a K-complex (VSW/KC), isolated VSW, and no evoked response (other). Evoked responses were averaged separately within these categories.Setting:Data were collected in the University of Melbourne Sleep Laboratory.Participants:Six young healthy male adults.Interventions:N/AMeasurements and Results:Data were recorded from 29 scalp sites referenced to linked ears. Mask pressure (Pm) and airflow were also recorded. Intra-thoracic pressure, as indicated by Pm, reached a more negative level following complete obstructions than brief occlusions. However, both types of respiratory stimuli elicited the two late latency components. Although latency varied across the two respiratory conditions in a manner consistent with the intra-thoracic pressure rise time differences, the elicitation characteristics and topographic distribution of these components did not vary across the two types of stimuli. In addition, an N350 was only present in the average for those categories that included VSWs, while an N550 was only present in those categories that contained K-complexes.Conclusions:Mid-inspiratory occlusions can be used as a model of obstructive events. VSWs contribute exclusively to the N350 component, while K-complexes contribute exclusively to the N550 component.