Effects of attention, distraction and sleep on CO2 laser evoked potentials related to C-fibers in humans

doi:10.1016/S1388-2457(02)00216-X

Clinical Neurophysiology

Volume 113, Issue 10, October 2002, Pages 1579-1585

https://doi.org/10.1016/S1388-2457(02)00216-X Get rights and content

Abstract

Objectives: The objective of this study is to evaluate the effects of attention, distraction and sleep on CO₂ laser-evoked potentials (LEP) relating to C-fibers (ultra-late LEP).

Methods: Non-painful CO₂ laser pulses were delivered to a tiny skin area of the dorsum of the right hand. Ultra-late LEP were recorded from 10 normal subjects in 5 different conditions: control (wakefulness), attention, distraction, drowsiness and sleep (stage 2).

Results: The amplitude of ultra-late LEP was slightly increased during attention and significantly decreased during distraction, relative to the control. The ultra-late LEP decreased much in amplitude or almost disappeared during sleep. However, significant differences in latency among the conditions were not found.

Conclusions: We confirmed that the brain responses relating to signals ascending through C-fibers were much affected by the level of consciousness, being consistent with the findings of late LEP relating to Aδ-fibers. This is the first study to indicate the important characteristics of ultra-late LEP relating to consciousness, suggesting that they include cognitive function and also that one has to be careful of the change in alertness when recording.

Introduction

Brief laser pulses have been applied to the skin to excite both small-myelinated Aδ-fibers and unmyelinated C-fibers (Bromm and Treede, 1984), but most previous studies reported findings on the former. The laser-evoked potentials (LEP) following painful CO₂ laser stimulation applied to the skin have been used for investigating the physiological functions of Aδ-fibers (see Reviews by Bromm and Lorenz, 1998, Chen et al., 1998a, Chen et al., 1998b, Kakigi et al., 2000, Treede et al., 2000). For example, the effects of attention and distraction on pain perception have been studied (Beydoun et al., 1993, Towell and Boyd, 1993, Siedenberg and Treede, 1996, Kanda et al., 1996, Zaslansky et al., 1996, Garcia-Larrea et al., 1997, Yamasaki et al., 1999). In these studies, the amplitude of the major positive component of late LEP was significantly reduced during distraction such as a calculation or memorization task (Beydoun et al., 1993, Garcia-Larrea et al., 1997, Yamasaki et al., 1999). Such an effect on Aδ-fibers was also found using painful high-intensity electrical stimuli (pain-related somatosensory-evoked potentials (SEP)) (Yamasaki et al., 2000). However, there have only been two reports on evoked cortical potentials in pain perception during sleep; one each on late LEP (Beydoun et al., 1993) and pain-related SEP (Naka and Kakigi, 1998), and both found that the amplitude remarkably decreased during sleep.

As compared to the late LEP relating to Aδ-fibers, cortical responses with a very long latency (ultra-late LEP) generated by signals ascending through C-fibers, probably relating to second pain are difficult to record. In the 1980s, several studies reported ultra-late LEP by acting C-fibers evoked selectively by conduction blockage of Aδ-fibers (Bromm and Treede, 1983, Bromm and Treede, 1984, Bromm and Treede, 1987a, Bromm and Treede, 1987b, Bromm et al., 1983), or in a patient with neurosyphilis whose myelinated fibers were abolished (Treede et al., 1988). Low intensity stimulation (Towell et al., 1996) or feed-back-controlled laser heat stimulation (Magerl et al., 1999) was also utilized, but with difficultly.

Recently, a new technique to record ultra-late LEP clearly and easily was established using non-painful CO₂ laser stimulation applied to a tiny area of the skin (Bragard et al., 1996, Opsommer, 1999, Opsommer et al., 1999, Opsommer et al., 2001, Tran et al., 2001, Tran et al., 2002a, Tran et al., 2002b, Qiu et al., 2001, Iannetti et al., 2001). Opsommer (1999) examined the changes of ultra-late LEP using the oddball paradigm, and found that the amplitude was enhanced when the subject's attention was given to the stimulus. However, there was no systematic study focusing on the change of ultra-late LEP caused by a change of attention or level of consciousness. In this study, therefore, we studied the effects of attention, distraction and sleep on ultra-late LEP to elucidate the characteristics of brain activities relating to second pain.

Section snippets

Subjects

Ten healthy volunteers participated in this study (8 males and two females). Their ages ranged from 26 to 49 (mean±SD: 37.7±6.2) years, height from 160 to 180 cm (mean±SD: 170.4±6.8), and weight from 50 to 80 kg (65.5±6.4). All 10 subjects were colleagues in our department and medical doctors. Therefore, they understood the aim of this study and declared that they were free from pain and sleep disturbance.

All participants gave their informed consent and this research was approved by the Ethical

Results

The ultra-late LEP, small negative component (N1) and a large positive component (P1), were recorded. We placed 3 electrodes at C3, C4 and Cz. Since the peak amplitude of N1–P1 was largest at the Cz in all subjects in the control condition, we mainly analyzed the results recorded there. We found no consistent new additional component at the C3 or C4 electrode. Since N1 was recorded in only 5 subjects in the control condition, we statistically analyzed the amplitude and latency of only P1 in

Discussion

There are two systems for nociceptive perception. One ascends through Aδ-nociceptors and Aδ-fibers relating to the first or sharp pain, while the other ascends through C-nociceptors and C-fibers relating to the second or burning pain. Both systems are, of course, very important in humans. However, due to a lack of suitable methods, there have been only a small number of reports on the C-fiber-related brain responses. An easy and reliable method for recording these responses would be applicable

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Sustained nociceptive stimuli have been shown to modulate the amplitude of ongoing neural oscillations in the theta, alpha and beta frequency bands at the frequency of stimulation, suggesting a relationship between these ongoing oscillations and pain perception. Yet, whether these ongoing oscillations are actually related to the pain experience remains unclear. If it were the case, then cognitive processes that are known to affect pain intensity should also affect these ongoing oscillations. To this end, we used electroencephalography (EEG) to investigate whether distraction – an attentional state known to affect pain perception – also modulates the amplitude of these neural oscillations. More specifically, we hypothesized that performing an unrelated arithmetic task during sustained nociceptive stimulation would lead to a decrease in the modulations of ongoing oscillations exerted by the stimulation. To assess the selectivity of this modulation for nociception, we compared the modulations of ongoing oscillations exerted by sustained periodic thermonociceptive and non-nociceptive vibrotactile stimulation (.2 Hz, 75 sec), while participants were either asked to solve an unrelated arithmetic task (distraction task) or received no specific instruction (baseline). The intensity of perception was significantly reduced by the arithmetic task in both the thermonociceptive and the vibrotactile modality, and the sustained periodic stimulation elicited a periodic response at the frequency of stimulation in both modalities. However, the distraction task did not show a differential effect for the two stimulation modalities in any of the frequency bands. The fact that, unlike pain perception, these oscillations did not appear to be affected by the task suggests that they are dissociable from pain perception. Whether a different task (leading to a stronger degree of distraction) could lead to different results is unclear.
Clinical neurophysiology of pain
2019, Handbook of Clinical Neurology
Citation Excerpt :
However, as aforementioned, under certain specific methodological conditions, it is possible to record specific cortical responses corresponding to C-fiber activation, especially using CO2 laser stimulation (Bromm et al., 1983). For example, the stimulated skin area can be covered by a thin aluminum plate pierced with tiny holes to enhance the chance of specifically stimulating C fibers, because they outnumber the Aδ fibers in the skin (higher C-related receptor density) (Bragard et al., 1996; Opsommer et al., 1999; Qiu et al., 2001, 2002, 2004; Tran et al., 2001, 2002a,b; Kakigi et al., 2003; Terhaar et al., 2011). A protocol of a similar kind has recently been applied to reliably produce specific C fiber-related LEPs with a low-energy diode laser (Azevedo et al., 2016).
Clinical neurophysiologic investigation of pain pathways in humans is based on specific techniques and approaches, since conventional methods of nerve conduction studies and somatosensory evoked potentials do not explore these pathways. The proposed techniques use various types of painful stimuli (thermal, laser, mechanical, or electrical) and various types of assessments (measurement of sensory thresholds, study of nerve fiber excitability, or recording of electromyographic reflexes or cortical potentials). The two main tests used in clinical practice are quantitative sensory testing and pain-related evoked potentials (PREPs). In particular, PREPs offer the possibility of an objective assessment of nociceptive pathways. Three types of PREPs can be distinguished depending on the type of stimulation used to evoke pain: laser-evoked potentials, contact heat evoked potentials, and intraepidermal electrical stimulation evoked potentials (IEEPs). These three techniques investigate both small-diameter peripheral nociceptive afferents (mainly Aδ nerve fibers) and spinothalamic tracts without theoretically being able to differentiate the level of lesion in the case of abnormal results. In routine clinical practice, PREP recording is a reliable method of investigation for objectifying the existence of a peripheral or central lesion or loss of function concerning the nociceptive pathways, but not the existence of pain. Other methods, such as nerve fiber excitability studies using microneurography, more directly reflect the activities of nociceptive axons in response to provoked pain, but without detecting or quantifying the presence of spontaneous pain. These methods are more often used in research or experimental study design. Thus, it should be kept in mind that most of the results of neurophysiologic investigation performed in clinical practice assess small fiber or spinothalamic tract lesions rather than the neuronal mechanisms directly at the origin of pain and they do not provide objective quantification of pain.
Reproducibility of contact heat evoked potentials (CHEPs) over a 6months interval
2013, Clinical Neurophysiology
Citation Excerpt :
With the intention to establish a noninvasive, objective measure of small fibre function, heat pain evoked potentials induced by laser or contact heat stimulation of primary afferent Aδ-fibres and recorded at the vertex have been a recent focus of research (Carmon et al., 1978; Bromm and Treede, 1987; Itskovich et al., 2000; Chen et al., 2001; Granovsky et al., 2005; Iannetti et al., 2006; Greffrath et al., 2007; Roberts et al., 2008). Ultralate C-fibre evoked potentials are inconstantly present (Bromm and Treede, 1987; Qiu et al., 2002; Truini et al., 2007; Pazzaglia and Valeriani, 2009). In patients with small fibre neuropathy, Aδ-fibre mediated laser-evoked potentials (LEPs) and contact-heat evoked potentials (CHEPs) either fail to be evoked or exhibit reduced amplitudes compared to controls (Treede et al., 2003; Pazzaglia and Valeriani, 2009; Cruccu et al., 2010; Chao et al., 2010; Casanova-Molla et al., 2011).
Contact heat evoked potentials (CHEPs) mediated by primary afferent Aδ-fibers can be recorded at the vertex. CHEPs are reduced in small fibre neuropathy and considered as a noninvasive measure of small fibre function. As long-term stability of CHEPs has not been examined, it is presently not clear if CHEPs may also be useful for following the course of small fibre neuropathy.
Here, we analyzed CHEPs from 60 healthy subjects recorded at two occasions separated by 6 months.
There was a systematic shift towards larger amplitudes (from 40.2 ± 13.8 μV to 53.3 ± 17.5 μV, p < 0.001) and towards shorter latencies (from 425.0 ± 28.8 ms to 387.2 ± 30.3 ms, p < 0.001) after six months, while CHEP areas were more constant over time.
The present results show that systematic changes of CHEP amplitudes and latencies may occur over time. Possible reasons include seasonal differences in skin conductivity for heat and psychological effects.
CHEP areas seem to be more stable over time than amplitudes or latencies, however, it remains to be determined if CHEP areas differentiate between subjects with lesions of the nociceptive system and healthy controls as reliably as CHEP amplitudes.
Cognitive aspects of nociception and pain. Bridging neurophysiology with cognitive psychology
2012, Neurophysiologie Clinique
Citation Excerpt :
The most recurrent result of these studies (except [82]) was a reduction of the magnitude of the vertex positivity of the ERPs (i.e. P2), which is supposed to mainly reflect the activity of the anterior cingulate cortex (ACC) [37], when attention was directed to the pain-unrelated task. This was the case both in studies that used nociceptive-specific stimuli delivered by laser heat stimulator [6,35,38,83,93,106,112,113] and studies that used non-specific electrocutaneous stimuli whose intensity was rated as painful [22,67,111]. This P2 amplitude reduction was accompanied by a reduction of pain rating, measured after each stimulation block [35,38,82] or after the experiment [67], except in the study by Zaslansky et al. [113] who did not find any modulation of pain rating.
The event-related brain potentials (ERPs) elicited by nociceptive stimuli are largely influenced by vigilance, emotion, alertness, and attention. Studies that specifically investigated the effects of cognition on nociceptive ERPs support the idea that most of these ERP components can be regarded as the neurophysiological indexes of the processes underlying detection and orientation of attention toward the eliciting stimulus. Such detection is determined both by the salience of the stimulus that makes it pop out from the environmental context (bottom-up capture of attention) and by its relevance according to the subject's goals and motivation (top-down attentional control). The fact that nociceptive ERPs are largely influenced by information from other sensory modalities such as vision and proprioception, as well as from motor preparation, suggests that these ERPs reflect a cortical system involved in the detection of potentially meaningful stimuli for the body, with the purpose to respond adequately to potential threats. In such a theoretical framework, pain is seen as an epiphenomenon of warning processes, encoded in multimodal and multiframe representations of the body, well suited to guide defensive actions. The findings here reviewed highlight that the ERPs elicited by selective activation of nociceptors may reflect an attentional gain apt to bridge a coherent perception of salient sensory events with action selection processes.
Les potentiels évoqués cérébraux (PE) induits par des stimuli nociceptifs sont largement influencés par la vigilance, les émotions, l’attention-alerte et l’attention sélective. Les études ayant spécifiquement exploré les effets de facteurs cognitifs sur les PE nociceptifs soutiennent l’idée selon laquelle la plupart des composantes de ces PE peuvent être considérées comme les indices neurophysiologiques des processus sous-jacents de détection et d’orientation de l’attention vers le stimulus évoquant. Cette détection est déterminée par la saillance du stimulus qui le rend particulièrement émergeant par rapport au contexte environnemental (capture ascendante de l’attention) et par sa pertinence par rapport aux objectifs cognitifs et à la motivation du sujet (contrôle attentionnel descendant). Le fait que les PE nociceptifs sont largement influencés par les informations provenant d’autres modalités sensorielles comme la vision et la proprioception, ainsi que par la préparation motrice suggère que ces PE reflètent un système cortical impliqué dans la détection des stimuli potentiellement significatifs pour l’organisme dans le but de répondre adéquatement aux menaces éventuelles. Dans un tel cadre théorique, la douleur est considérée comme un épiphénomène des processus d’alerte, intégrés dans des représentations multimodales et multi-référentielles du corps dont le but est de guider la réalisation des comportements de défense. Les données présentées dans cet article soulignent que les PE obtenus en réponses à des stimulations sélectives des nocicepteurs peuvent représenter l’activité des mécanismes de contrôle du gain attentionnel permettant de coordonner de façon cohérente la perception d’événements sensoriels saillants et la sélection de la réponse.
Pain and sleep: From reaction to action
2012, Neurophysiologie Clinique
Citation Excerpt :
Even in the absence of arousal/awakening, the cortical processing of nociceptive stimuli is partly preserved during sleep nociceptive-specific brain responses can be recorded using cutaneous infrared laser stimuli, which specifically activate thin myelinated (A-delta) and unmyelinated (C) fibres [9] and yield cerebral potentials reflecting cortical pain processing [18,46]. Two studies performed during short naps suggested a loss of cortical potentials to stimulation of either A-delta [6] or C-fibres [49] during drowsiness and light sleep. More recently, in an all-night sleep study, Bastuji et al. [3] showed that cortical responses to nociceptive laser stimuli remained present during all sleep stages.
Sleep disruption by painful stimuli is frequently observed both in clinical and experimental conditions. Nociceptive stimuli produce significantly more arousals (30% of stimuli) than non-nociceptive ones. However, even if they do not interrupt sleep, they can trigger a variety of other reactions. Reflex behaviours in response to nociceptive stimuli can be observed during all sleep stages, and are more likely to occur in association with an arousal than alone. Cardiac activation represents a robust sympathetically driven effect preserved whatever the state of vigilance, even if its magnitude can be modulated by a concomitant cortical arousal. Not withstanding these reactions, incorporation of nociceptive stimuli into dream content remains limited. At cortical level, laser-evoked potential studies demonstrate that the processing of nociceptive stimulations is partly conserved during all sleep stages. Furthermore, when nociceptive stimulations interrupt sleep, the cortical response presents a late component suggesting that the stimulation has to be cognitively processed in order to produce a subsequent arousal. More complex reactions to nociceptive stimulations were occasionally reported. In this context, an epileptic patient with intracerebral electrodes implanted for therapeutic purposes allowed us extending these observations. This patient exhibited finger lifts in response to stimulations delivered during paradoxical (REM) sleep. This motor reaction was previously used during wakefulness to indicate that the stimulation had been perceived. When these finger lifts occurred a systematic re-activation of the anterior cingulate preceded each movement. This observation suggests that during PS, not only the processing of sensory inputs but also the capacity for the sleeper to intentionally indicate his perception could be preserved under particular circumstances.
L’interruption du sommeil par la douleur est fréquemment observée en conditions clinique et expérimentale. Des stimuli nociceptifs provoquent significativement plus de réveils que des stimuli non douloureux, et même s’ils n’interrompent pas le sommeil, ils peuvent induire d’autres types de réactions. Ainsi, des réflexes comportementaux, pouvant être observés dans tous les stades de sommeil, sont le plus souvent associés à des éveils. La réactivation cardiaque sympathique est présente, quel que soit le stade de vigilance, mais son amplitude est modulée par la concomitance d’un éveil cortical. En revanche, l’incorporation des stimuli nociceptifs dans le contenu onirique reste peu fréquente. Les études par potentiels évoqués au laser montrent que le traitement cortical de l’information nociceptive est partiellement maintenu au cours de tous les stades de sommeil. De plus, lorsque les stimulations interrompent le sommeil, la réponse corticale comporte une composante tardive suggérant qu’un traitement cognitif est nécessaire pour que cette stimulation induise par la suite un éveil. Des réactions plus complexes ont été occasionnellement rapportées. Dans ce contexte, nous présentons le cas d’une patiente épileptique, enregistrée en bilan préchirurgical à l’aide d’électrodes intracérébrales, qui au cours du sommeil paradoxal a spontanément effectué une consigne apprise à l’éveil, à savoir lever son index en réponse aux stimulations nociceptives. Ce mouvement du doigt était précédé d’une activation systématique du cortex cingulaire antérieur. Cela suggère qu’au cours du sommeil paradoxal, le traitement de l’information sensorielle est préservé mais également que le dormeur peut garder la possibilité d’indiquer intentionnellement sa perception.
Evidence of different spinal pathways for the warmth evoked potentials
2011, Clinical Neurophysiology
To investigate the presence of multiple spinothalamic pathways for warmth in the human spinal cord.
Laser evoked potentials to C-fiber stimulation (C-LEPs) were recorded in 15 healthy subjects after warmth stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels. This method allowed us to calculate the spinal conduction velocity (CV) in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different C-LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the C-N1 potential, generated in the second somatosensory (SII) area, and the late C-P2 response, generated in the anterior cingulate cortex (ACC).
The calculated CV of the spinal fibers generating the C-N1 potential (around 2.5 m/s) was significantly different (p < 0.01) from the one of the pathway producing the P2 response (around 1.4 m/s).
Our results suggest that the C-N1 and the C-P2 components are generated by two parallel spinal pathways.
Warmth sensation is subserved by parallel spinothalamic pathways, one probably reaching the SII area, the other the ACC.

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Effects of attention, distraction and sleep on CO2 laser evoked potentials related to C-fibers in humans

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Electroenceph clin Neurophysiol

Neurosci Lett

Electroenceph clin Neurophysiol

Neurosci Lett

Pain Forum

Pain Forum

Electroenceph clin Neurophysiol

Pain

Neurophysiol Clin

Neurosci Lett

Pain

Neurosci Lett

Electroenceph clin Neurophysiol

Pain

Pain

Neurosci Lett

Pain

Brain Res Cogn Brain Res

Brain Res Cogn Brain Res

Electroenceph clin Neurophysiol

Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography

Exp Brain Res

Effects of attention, distraction and sleep on CO₂ laser evoked potentials related to C-fibers in humans