Laser-evoked Brain Potentials Research Articles

Influence of skin type and laser wavelength on laser-evoked potentials.

Infrared laser stimulation is a valuable tool in pain research, its primary application being the recording of laser-evoked brain potentials (LEPs). Different types of laser stimulators, varying in their skin penetrance, are likely to have a large influence on the LEPs, when stimulating different skin types. The aim of this study was to investigate how LEPs depend on laser type and skin location. Two different laser stimulators (CO2 and Nd:YAP) were used to compare LEPs in healthy subjects. Stimuli were delivered to the hand dorsum and palm to investigate the effects of skin type on the evoked responses. Stimulus-evoked brain responses were recorded using EEG and perceived intensity ratings were recorded. Computational modelling was used to investigate the observed differences. LEPs evoked by stimulation of the hairy skin were similar between CO2 and Nd:YAP stimulation. In contrast, LEPs elicited from the palm were markedly different and barely present for CO2 stimulation. There was a significant interaction between laser type and skin type (RM-ANOVA, p < 0.05) likely due to smaller CO2 LEPs in the palm. CO2 stimuli to the palm also elicited significantly lower perceived intensities. The computational model showed that the observed differences were explainable by the laser absorption characteristics and skin thickness affecting the temperature profile at the dermo-epidermal junction (DEJ). This study shows that LEP elicitation depends on the combination of laser penetrance and skin type. Low penetrance stimuli, from a CO2 laser, elicited significantly lower LEPs and perceived intensities in the palm. This study showed that the elicitation of laser-evoked potentials in healthy humans greatly depends on the combination of laser stimulator type and skin type. It was shown that high penetrance laser stimuli are capable of eliciting responses in both hairy and glabrous skin, whereas low penetrance stimuli barely elicited responses from the glabrous skin. Computational modelling was used to demonstrate that the results could be fully explained by the combination of laser type and skin thickness.

IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG)

BackgroundIMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity.MethodsThis is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory.DiscussionLEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification.Trial registrationThis trial was registered 25/06/2019 in EudraCT (2019%2D%2D001204-37).

Fibromyalgia syndrome-A laser-evoked potentials study unsupportive of small nerve fibre involvement.

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by widespread pain and a variety of non-pain symptoms. Central sensitivity phenomena are found consistently in FMS. Additionally, several researchers proclaimed that a subgroup of FMS patients may present with unrecognized peripheral small fibre neuropathy (SFN). Laser-evoked brain potentials (LEP) are considered as a reliable method for the functional assessment of the thermo-nociceptive system, including the evaluation of SFN. The aim of this retrospective study was to estimate the prevalence of thermo-nociceptive system dysfunction based on LEPs in FMS. LEP recordings of 92 FMS patients and 39 age and gender-matched healthy controls were selected from a database collected between 2003 and 2012 with standardized settings for laser stimulation and EEG recording. The N1, N2 and P2 LEP components were identified and characterized by peak latency and amplitude. None of the FMS patients showed signs of loss of function of the nociceptive responses evoked by A δ-nociceptor activation, compared to healthy controls. 6.5% of the FMS patients had N2-P2 peak-to-peak amplitudes above the upper limit of the 99%-confidence interval. N2-P2 peak-to-peak amplitudes were negatively correlated with age, without age-related differences between groups. The characteristic signs of a damaged thermo-nociceptive system as revealed by LEPs were absent in this large cohort of FMS patients. The present research does not support the hypothesis that small fibre neuropathy is a significant contributor to the pathophysiology of FMS.

Simultaneous Recordings of Cortical Local Field Potentials and Electrocorticograms in Response to Nociceptive Laser Stimuli from Freely Moving Rats.

Electrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.e., electrocorticogram [ECoG] and scalp electroencephalogram [scalp EEG]) and inside the brain (i.e., local field potential [LFP]). To address this issue, we present here an animal protocol using freely moving rats. This protocol is composed of three main procedures: (1) animal preparation and surgical procedures, (2) a simultaneous recording of ECoG and LFP in response to nociceptive laser stimuli, and (3) data analysis and feature extraction. Specifically, with the help of a 3D-printed protective shell, both ECoG and LFP electrodes implanted on the rat's skull were securely held together. During data collection, laser pulses were delivered on the rat's forepaws through gaps in the bottom of the chamber when the animal was in spontaneous stillness. Ongoing white noise was played to avoid the activation of the auditory system by the laser-generated ultrasounds. As a consequence, only nociceptive responses were selectively recorded. Using the standard analytical procedures (e.g., band-pass filtering, epoch extraction, and baseline correction) to extract stimulus-related brain responses, we obtained results showing that LEPs with a high signal-to-noise ratio were simultaneously recorded from ECoG and LFP electrodes. This methodology makes the simultaneous recording of ECoG and LFP activities possible, which provides a bridge of electrocortical signals at the mesoscopic and macroscopic levels, thereby facilitating the investigation of nociceptive information processing in the brain.

Psychophysical and electrophysiological evidence for nociceptive dysfunction in complex regional pain syndrome

The aim of this study was to assess the function of the thermo-nociceptive system in 25 patients with long-lasting, medium-to-severe refractory complex regional pain syndrome (CRPS)-1 using behavioral (detection rates and reaction times) and electrophysiological (event-related brain potentials) responses to brief (50milliseconds) and intense (suprathreshold for Aδ-nociceptors) carbon dioxide laser stimuli delivered to the affected and contralateral limbs, and by comparing these responses to the responses obtained in the left and right limbs of age- and sex-matched healthy controls. Compared with healthy controls and compared with the contralateral limb, the detection rate of pricking pain related to the activation of Aδ-fibers was markedly reduced at the affected limb. Furthermore, reaction times were substantially prolonged (>100milliseconds in 84% of patients and >300milliseconds in 50% of patients). Finally, the N2 and P2 waves of laser-evoked brain potentials were significantly reduced in amplitude, and their latencies were significantly increased. Taken together, our results show that in the majority of patients with chronic CRPS-1, thermo-nociceptive pathways are dysfunctional. A number of pathological mechanisms involving the peripheral nervous system and/or the central nervous system could explain our results. However, the primary or secondary nature of these observed changes remains an open question.

Reliable EEG responses to the selective activation of C-fibre afferents using a temperature-controlled infrared laser stimulator in conjunction with an adaptive staircase algorithm

Brain responses to the activation of C-fibres are obtained only if the co-activation of Aδ-fibres is avoided. Methods to activate C-fibres selectively have been proposed, but are unreliable or difficult to implement. Here, we propose an approach combining a new laser stimulator to generate constant-temperature heat pulses with an adaptive paradigm to maintain stimulus temperature above the threshold of C-fibres but below that of Aδ-fibres, and examine whether this approach can be used to record reliable C-fibre laser-evoked brain potentials. Brief CO2 laser stimuli were delivered to the hand and foot dorsum of 10 healthy subjects. The stimuli were generated using a closed-loop control of laser power by an online monitoring of target skin temperature. The adaptive algorithm, using reaction times to distinguish between late detections indicating selective activation of unmyelinated C-fibres and early detections indicating co-activation of myelinated Aδ-fibres, allowed increasing the likelihood of selectively activating C-fibres. Reliable individual-level electroencephalogram (EEG) responses were identified, both in the time domain (hand: N2: 704±179ms, P2: 984±149ms; foot: N2: 1314±171ms, P2: 1716±171ms) and the time-frequency (TF) domain. Using a control dataset in which no stimuli were delivered, a Receiver Operating Characteristics analysis showed that the magnitude of the phase-locked EEG response corresponding to the N2-P2, objectively quantified in the TF domain, discriminated between absence vs presence of C-fibre responses with a high sensitivity (hand: 85%, foot: 80%) and specificity (hand: 90%, foot: 75%). This approach could thus be particularly useful for the diagnostic workup of small-fibre neuropathies and neuropathic pain.

Dyspnea-pain counterirritation induced by inspiratory threshold loading: a laser-evoked potentials study

experimentally induced dyspnea of the work/effort type inhibits, in a top-down manner, the spinal transmission of nociceptive inputs (dyspnea-pain counterirritation). Previous studies have demonstrated that this inhibition can be assessed by measuring the nociceptive flexion reflex (RIII). However, its clinical application is limited because of the strong discomfort associated with the electrical stimuli required to elicit the RIII reflex. we examined whether the dyspnea-pain counterirritation phenomenon can be evaluated by measuring the effect of work/effort type dyspnea on the magnitude of laser-evoked brain potentials (LEPs). 10 normal male volunteers were studied (age: 19-30 years). LEPs were elicited using a CO(2) laser stimulator delivering 10- to 15-ms stimuli of 6 ± 0.7 W over a 12.5 mm(2) area. The EEG was recorded using nine scalp channels. Non-nociceptive somatosensory-evoked potentials (SEPs) served as control. LEPs and SEPs were recorded before, during, and after 10 min of experimentally induced dyspnea [inspiratory threshold loading (ITL)]. pain caused by the nociceptive laser stimulus was mild. ITL consistently induced dyspnea, mostly of the "excessive effort" type. Amplitude of the N2-P2 wave of LEPs decreased by 37.6 ± 13.8% during ITL and was significantly correlated with the intensity of dyspnea [r = 0.66, CI 95% (0.08-0.92, P = 0.0319)]. In contrast, ITL had no effect on the magnitude of non-nociceptive SEPs. experimentally induced dyspnea of the work/effort type reduces the magnitude of LEPs. This reduction correlates with the intensity of dyspnea. The recording of LEPs could constitute a clinically applicable approach to assess the dyspnea-pain counterirritation phenomenon in patients.

The primary somatosensory cortex largely contributes to the early part of the cortical response elicited by nociceptive stimuli

Research on the cortical sources of nociceptive laser-evoked brain potentials (LEPs) began almost two decades ago (Tarkka and Treede, 1993). Whereas there is a large consensus on the sources of the late part of the LEP waveform (N2 and P2 waves), the relative contribution of the primary somatosensory cortex (S1) to the early part of the LEP waveform (N1 wave) is still debated. To address this issue we recorded LEPs elicited by the stimulation of four limbs in a large population (n=35). Early LEP generators were estimated both at single-subject and group level, using three different approaches: distributed source analysis, dipolar source modeling, and probabilistic independent component analysis (ICA). We show that the scalp distribution of the earliest LEP response to hand stimulation was maximal over the central-parietal electrodes contralateral to the stimulated side, while that of the earliest LEP response to foot stimulation was maximal over the central-parietal midline electrodes. Crucially, all three approaches indicated hand and foot S1 areas as generators of the earliest LEP response. Altogether, these findings indicate that the earliest part of the scalp response elicited by a selective nociceptive stimulus is largely explained by activity in the contralateral S1, with negligible contribution from the secondary somatosensory cortex (S2).

A new Kalman filter approach for the estimation of high-dimensional time-variant multivariate AR models and its application in analysis of laser-evoked brain potentials

In this methodological study we present a new version of a Kalman filter technique to estimate high-dimensional time-variant (tv) multivariate autoregressive (tvMVAR) models. It is based on an extension of the state-space model for a multivariate time series to a matrix-state-space model for multi-trial multivariate time series. The result is a general linear Kalman filter (GLKF). The GLKF enables a tvMVAR model estimation which was applied for interaction analysis of simulated data and high-dimensional multi-trial laser-evoked brain potentials (LEP). The tv partial Granger causality index (tvpGCI) was used to investigate the interaction patterns between LEPs derived from an experiment with noxious laser stimulation. First, the new approach was compared with the multi-trial version of the recursive least squares (RLS) algorithm with forgetting factor (Moller et al., 2001) by using 24 distinct electrodes. The RLS failed for a channel number (dimension) higher than 24. Secondly, the analysis was repeated by using all 58 electrodes and the similarities and differences of the GCI-based interaction patterns are discussed. It can be demonstrated that the application of high-dimensional tvMVAR modelling will contribute to a better understanding of the relationship between structure and function.

A novel approach for enhancing the signal-to-noise ratio and detecting automatically event-related potentials (ERPs) in single trials

Brief radiant laser pulses can be used to activate cutaneous Aδ and C nociceptors selectively and elicit a number of transient brain responses in the ongoing EEG (N1, N2 and P2 waves of laser-evoked brain potentials, LEPs). Despite its physiological and clinical relevance, the early-latency N1 wave of LEPs is often difficult to measure reliably, because of its small signal-to-noise ratio (SNR), thus producing unavoidable biases in the interpretation of the results. Here, we aimed to develop a method to enhance the SNR of the N1 wave and measure its peak latency and amplitude in both average and single-trial waveforms. We obtained four main findings. First, we suggest that the N1 wave can be better detected using a central-frontal montage (Cc-Fz), as compared to the recommended temporal–frontal montage (Tc-Fz). Second, we show that the N1 wave is optimally detected when the neural activities underlying the N2 wave, which interfere with the scalp expression of the N1 wave, are preliminary isolated and removed using independent component analysis (ICA). Third, we show that after these N2-related activities are removed, the SNR of the N1 wave can be further enhanced using a novel approach based on wavelet filtering. Fourth, we provide quantitative evidence that a multiple linear regression approach can be applied to these filtered waveforms to obtain an automatic, reliable and unbiased estimate of the peak latency and amplitude of the N1 wave, both in average and single-trial waveforms.

Are There Nociceptive-Specific Brain Potentials? Reply to Baumgärtner and Treede

reply: In a recent commentary, Baumgartner and Treede question the conclusion of our recent study, in which we show that laser-evoked brain potentials (LEPs) are not able to isolate nociceptive-specific cortical processing ([Mouraux and Iannetti 2009][1]). Here, we will show that the three points

Are There Nociceptive-Specific Brain Potentials?

to the editor: In their study on factor analysis of brain responses to different stimulus modalities, [Mouraux and Iannetti (2009)][1] claimed that laser-evoked brain potentials do not reflect nociceptive-specific neural activity, although laser radiant heat pulses provide a purely nociceptive input

202 Comparison of quantitative sensory testing and laser-evoked brain potentials in syringomyelia patients

202 Comparison of quantitative sensory testing and laser-evoked brain potentials in syringomyelia patients

Are laser-evoked brain potentials modulated by attending to first or second pain?

By co-activating Aδ- and C-nociceptors, a brief and intense infrared laser stimulus may produce a double sensation referred to as ‘first’ and ‘second’ pain, evoke late laser-evoked brain potentials (LEPs) related to the processing of Aδ-fiber input, but fails to evoke any consistent activity related to C-fibers. Yet, ultra-late LEPs may be recorded if C-nociceptors are activated in isolation. Bromm and Treede (1985) reported that if a subject selectively focused his attention towards second pain, co-activation of Aδ- and C-nociceptors could elicit both late and ultra-late LEPs (Bromm B, Treede RD. Electroencephalogr Clin Neurophysiol 1985;61). They hypothesized that for C-fiber input to elicit consistent ultra-late LEPs, attention must be specifically focused towards that sensory channel. However, the significance of this study was limited by the fact it relied on results of a single subject and used latency-correction algorithms. In an attempt to replicate these findings, this study examined LEPs recorded while trained subjects focused their attention either towards first pain or towards second pain. Whether or not subjects attended second pain, laser stimuli co-activating Aδ- and C-nociceptors failed to elicit ultra-late LEPs, indicating that focusing attention towards C-fiber sensory input is not a sufficient condition for that input to evoke LEPs. However, selectively attending to first or second pain significantly modulated Aδ-fiber related late LEPs. When subjects attended first pain, a late parietal P3 component was recorded, possibly related to task closure. When subjects attended second pain, a prefrontal positive enhancement of the P2 component was observed. Whether it could reflect brain processes related to response-inhibition is discussed.

Simultaneous recording of laser-evoked brain potentials and continuous, high-field functional magnetic resonance imaging in humans

Simultaneous recording of event-related electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) responses has the potential to provide information on how the human brain reacts to an external stimulus with unique spatial and temporal resolution. However, in most studies combining the two techniques, the acquisition of functional MR images has been interleaved with the recording of evoked potentials. In this study we investigated the feasibility of recording pain-related evoked potentials during continuous and simultaneous collection of blood oxygen level-dependent (BOLD) functional MR images at 3 T. Brain potentials were elicited by selective stimulation of cutaneous Aδ and C nociceptors using brief radiant laser pulses (laser-evoked potentials, LEPs). MR-induced artifacts on EEG data were removed using a novel algorithm. Latencies, amplitudes, and scalp distribution of LEPs recorded during fMRI were not significantly different from those recorded in a control session outside of the MR scanner using the same equipment and experimental design. Stability tests confirmed that MR-image quality was not impaired by the evoked potential recording, beyond signal loss related to magnetic susceptibility differences local to the electrodes. fMRI results were consistent with our previous studies of brain activity in response to nociceptive stimulation. These results demonstrate the feasibility of recording reliable pain-related LEPs and fMRI responses simultaneously. Because LEPs collected during fMRI and those collected in a control session show remarkable similarity, for many experimental designs the integration of LEP and fMRI data collected in separate, single-modality acquisitions may be appropriate. Truly simultaneous recording of LEPs and fMRI is still desirable in specific experimental conditions, such as single-trial, learning, and pharmacological studies.

Ultra-Late Evoked Potentials Following Stimulation of Tiny Skin Surface Areas in Humans

C-fiber input to the central nervous system is considered to represent an important antecedent for the experience of secondary pain. Clinically more important, this input is suggested to play a major role in the chronification of pain. However, there are only limited possibilities to investigate this input selectively, i.e., without simultaneous activation of C-fibers. One method that allows the selective activation of cutaneous A- and C-fiber afferents in humans is the stimulation of tiny skin surface areas (about 0.23mm2). We used this method for stimulation of the dorsum of the left hand and the left foot using a thulium-YAG laser stimulator. 12 volunteers were stimulated while EEG were recorded simultaneously. Additionally, reaction times (RTs), ratings of the perceived intensity of the stimulus, and descriptions of the perceptions (e.g., warm, burning) were registered for each single stimulus. Laser-evoked brain potentials (LEPs) were calculated for shorter and longer RTs on the basis of individual distributions of RTs and interpreted as belonging to A- and C-fibers, respectively. LEPs calculated on the basis of the stimulation of A of shorter RTs showing a waveform typical for late LEPs, i.e.,, a negative peak around 220 ms and a positive peak around 320, ms both with a maximum in Cz. As expected, latencies were longer for foot as compared to hand stimulation. LEPs calculated on the basis of longer RTs show a waveform typical for ultra-late LEPs with two components irrespective from the place of stimulation. A negative component peaked around 920 ms whereas a positive component peaked around 1,120 ms. Both components had their maximum at electrode Cz. As expected, latencies were again longer for foot as compared to hand stimulation. However, a different A- and C-fiber stimulation was found for the hand vs. foot distribution of A stimulation. C-fiber responses were significantly more often observed to stimulation to the hand as compared to stimulation to the foot. In conclusion, Tm-YAG laser stimulation of tiny skin surface areas offers an opportunity to investigate central nervous responses to selective stimulation of A- and C-fibers in humans at different sites of the body. Supported by IZKF Jena.

Refractoriness cannot explain why C-fiber laser-evoked brain potentials are recorded only if concomitant Aδ-fiber activation is avoided

Co-activation of Aδ- and C-fiber nociceptors by brief cutaneous laser heat stimuli may induce a dual sensation composed of first and second pain but evokes only a single, Aδ-fiber related, late laser-evoked potential (LEP). Yet, when concomitant activation of Aδ-nociceptors is avoided, C-nociceptor activation evokes an ultra-late LEP. As cumulating evidence indicates that late and ultra-late LEPs may share common generators, investigators have hypothesized that when Aδ-fibers trigger a late LEP, the later arriving C-fiber afferent volley cannot trigger an ultra-late LEP because underlying generators are in a ‘refractory state’. Better understanding of these interactions could have important consequences regarding the functional significance of LEPs. Therefore, this hypothesis was tested by applying two consecutive laser stimuli to the hand dorsum such as to produce a second Aδ-nociceptor afferent volley arriving at generators during their expected ‘refractory period’. Results showed that late LEPs evoked by the second stimulus were not altered and consequently that this hypothesis does not hold. In addition, when stimuli ended the sensory detection task, an ample P600 component was recorded. Studies have shown that this component is probably related to the P3b component described in other sensory modalities. This result provides support to the ‘context closure’ model hypothesizing that this component reflects the closure of information processing occurring when expectations are terminated. Altogether, these results suggest that late and ultra-late LEPs reflect very general processes, which are mainly related to detection and orientation and constitute only a fraction of the central processing of both nociceptive inputs.

Contribution of attentional and cognitive factors to laser evoked brain potentials

Painful stimuli delivered by infrared laser stimulators elicit laser-evoked potentials (LEP) or magnetic fields in respective electroencephalogram (EEG) and magnetoencephalogram (MEG). Evidence is reviewed that LEP represent a series of event-related potentials (ERP) that depend on vigilance and arousal, selective spatial attention and contextual task variables. Paradigms adopted from other stimulus modalities in the assessment of attention and cognition in ERP and applied to LEP allow the view that middle-latency (N1) and long latency (N2–P2) components of LEP can be overlapped or supplemented by endogenous components such as the processing negativity and distinct members (P3a and P3b) of the “P300” activities, each of which is considered in detail in this review. This composite entity needs to be considered when LEP are experimentally or clinically used in the assessment of sensory and cognitive phenomena and abnormalities of pain sensation.

Maturational changes in the thermoalgesic system in humans from childhood to adulthood revealed by CO 2 laser evoked brain potentials following cutaneous heat stimuli

Possible maturational changes in the thermoalgesic system were studied by reaction times (RT) and late (Adelta-fibre) laser evoked potentials (LEPs) following CO 2 laser heat stimulation of the hand in healthy children ( n=12) and young adults ( n=12). In children (10±2 years) LEPs presented a negative-positive complex with maximum amplitude (peak-to-peak 71±35 μV) at the vertex and latencies of 248±82 and 433±104 ms, respectively. As compared to adults (24±3 years), children had a significant increased peak-to-peak amplitude (+25.7μV; P=0.03) although no difference in latencies and topography. Median RT (710 ms) was also significantly increased (+312 ms; P<0.005) in children. A decrease in RT and late LEP amplitude from childhood to adulthood may reflect aspects of maturation in sensory processing of the thermoalgesic system.

Determination of nerve conduction velocity of C-fibres in humans from thermal thresholds to contact heat (thermode) and from evoked brain potentials to radiant heat (CO 2 laser)

This study was designed to estimate and compare nerve conduction velocity (NCV) of cutaneous heat-sensitive C-fibres obtained using two methods. The first is a method based on reaction times to different rates of temperature change produced by a large contact thermode (Thermotest). The second is a novel method based on ultra-late-evoked brain potentials to CO2 laser stimuli with tiny beam sections (< 0.25 mm2), allowing selective and direct activation of very slow conducting afferents. Both methods were applied on three sites of the right leg (foot, knee and thigh) of ten healthy subjects. When based on the reaction times to contact heat, NCV estimations were 0.4 +/- 0.22 m/s for the proximal segment (knee-thigh) and 0.6 +/- 0.23 m/s for the distal segment (foot-knee). When based on the difference in latency of the ultra-late positivity of laser-evoked brain potentials, NCV estimations were respectively 1.4 +/- 0.77 m/s and 1.2 +/- 0.55 m/s. For both methods, the difference in NCV between proximal and distal limb segments was not significant. Although both methods give NCV estimations within the range of C-fibres, the systematic difference between NCV obtained from each method may result from the activation of subpopulations of C-fibres with different NCV depending on the method of stimulation (low-threshold thermal receptors by the thermode and thermal nociceptors by the CO2 laser). Considering the difficulty of investigating peripheral fibres with slow conduction velocities (C-fibres) in humans, the methods used in the present study may be useful tools in both experimental and clinical situations.