Léon Plaghki

Impaired selective attention in chronic pain patients

Several recent studies have suggested that cognitive complaints among chronic pain patients could result from an interference between ongoing pain and mental tasks, as they share common and limited attentional resources. This study was intended to further explore that presumed relationship between chronic pain and attentional disorders. For this purpose, a more sensitive version of the conventional colour‐word Stroop task, with four subtasks of increasing difficulty, was used in a group of 33 consecutive patients with chronic nonmalignant pain and a group of 20 healthy subjects as controls. This task assesses specifically selective attention. Since the Stroop task is sensitive to dysthymic states, levels of anxiety and depression were also assessed in chronic pain patients.

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 (CO2 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.

Nociceptive steady-state evoked potentials elicited by rapid periodic thermal stimulation of cutaneous nociceptors

The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response known as steady-state evoked potential (SS-EP). In the somatosensory, visual, and auditory modalities, SS-EPs are considered to constitute an electrophysiological correlate of cortical sensory networks resonating at the frequency of stimulation. In the present study, we describe and characterize, for the first time, SS-EPs elicited by the selective activation of skin nociceptors in humans. The stimulation consisted of 2.3-s-long trains of 16 identical infrared laser pulses (frequency, 7 Hz), applied to the dorsum of the left and right hand and foot. Two different stimulation energies were used. The low energy activated only C-nociceptors, whereas the high energy activated both Aδ- and C-nociceptors. Innocuous electrical stimulation of large-diameter Aβ-fibers involved in the perception of touch and vibration was used as control. The high-energy nociceptive stimulus elicited a consistent SS-EP, related to the activation of Aδ-nociceptors. Regardless of stimulus location, the scalp topography of this response was maximal at the vertex. This was noticeably different from the scalp topography of the SS-EPs elicited by innocuous vibrotactile stimulation, which displayed a clear maximum over the parietal region contralateral to the stimulated side. Therefore, we hypothesize that the SS-EPs elicited by the rapid periodic thermal activation of nociceptors may reflect the activation of a network that is preferentially involved in processing nociceptive input and may thus provide some important insight into the cortical processes generating painful percepts.

Systematic overview of the pharmacological management of postherpetic neuralgia. An evaluation of the clinical value of critically selected drug treatments based on efficacy and safety outcomes from randomized controlled studies.

Objective: This study systematically reviews current evidence on drug treatments commonly used in postherpetic neuralgia. Methods: Randomized controlled trials were critically selected using predefined search criteria. Efficacy was evaluated as percentage of improvement in pain intensity between baseline and endpoint, tolerability by number of study discontinuations because of adverse events and incidence of adverse events. Results: Currently published trials enrolled different patient populations and small patient numbers. The great variability in doses, titration schemes, designs and washout periods together with other design flaws made comparison between different studies scientifically impossible. Conclusions: There is a real need for well-performed clinical trials with standardization in design and reporting. Development of adequate and validated questionnaires for evaluation and comparison of efficacy and safety of treatments is also needed. Based on the evaluation of individual studies, it is concluded that only gabapentin is studied in large (over 200 patients), placebo-controlled studies showing good efficacy and safety.

Shielding cognition from nociception with working memory.

Because pain often signals the occurrence of potential tissue damage, nociceptive stimuli have the capacity to capture attention and interfere with ongoing cognitive activities. Working memory is known to guide the orientation of attention by maintaining goal priorities active during the achievement of a task. This study investigated whether the cortical processing of nociceptive stimuli and their ability to capture attention are under the control of working memory. Event-related brain potentials (ERPs) were recorded while participants performed primary tasks on visual targets that required or did not require rehearsal in working memory (1-back vs 0-back conditions). The visual targets were shortly preceded by task-irrelevant tactile stimuli. Occasionally, in order to distract the participants, the tactile stimuli were replaced by novel nociceptive stimuli. In the 0-back conditions, task performance was disrupted by the occurrence of the nociceptive distracters, as reflected by the increased reaction times in trials with novel nociceptive distracters as compared to trials with standard tactile distracters. In the 1-back conditions, such a difference disappeared suggesting that attentional capture and task disruption induced by nociceptive distracters were suppressed by working memory, regardless of task demands. Most importantly, in the conditions involving working memory, the magnitude of nociceptive ERPs, including ERP components at early latency, were significantly reduced. This indicates that working memory is able to modulate the cortical processing of nociceptive input already at its earliest stages, and could explain why working memory reduces consequently ability of nociceptive stimuli to capture attention and disrupt performance of the primary task. It is concluded that protecting cognitive processing against pain interference is best guaranteed by keeping out of working memory pain-related information.

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

Summary Psychophysical and electrophysiological assessments of nociception using laser stimulation reveal a marked dysfunction of thermo‐nociceptive pathways in the affected limb of patients with chronic complex regional pain syndrome. Abstract 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 (50 milliseconds) and intense (suprathreshold for A&dgr;‐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 A&dgr;‐fibers was markedly reduced at the affected limb. Furthermore, reaction times were substantially prolonged (>100 milliseconds in 84% of patients and >300 milliseconds 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.

Unmasking the obligatory components of nociceptive event-related brain potentials.

It has been hypothesized that the human cortical responses to nociceptive and nonnociceptive somatosensory inputs differ. Supporting this view, somatosensory-evoked potentials (SEPs) elicited by thermal nociceptive stimuli have been suggested to originate from areas 1 and 2 of the contralateral primary somatosensory (S1), operculo-insular, and cingulate cortices, whereas the early components of nonnociceptive SEPs mainly originate from area 3b of S1. However, to avoid producing a burn lesion, and sensitize or fatigue nociceptors, thermonociceptive SEPs are typically obtained by delivering a small number of stimuli with a large and variable interstimulus interval (ISI). In contrast, the early components of nonnociceptive SEPs are usually obtained by applying many stimuli at a rapid rate. Hence, previously reported differences between nociceptive and nonnociceptive SEPs could be due to differences in signal-to-noise ratio and/or differences in the contribution of cognitive processes related, for example, to arousal and attention. Here, using intraepidermal electrical stimulation to selectively activate Aδ-nociceptors at a fast and constant 1-s ISI, we found that the nociceptive SEPs obtained with a long ISI are no longer identified, indicating that these responses are not obligatory for nociception. Furthermore, using a blind source separation, we found that, unlike the obligatory components of nonnociceptive SEPs, the obligatory components of nociceptive SEPs do not receive a significant contribution from a contralateral source possibly originating from S1. Instead, they were best explained by sources compatible with bilateral operculo-insular and/or cingulate locations. Taken together, our results indicate that the obligatory components of nociceptive and nonnociceptive SEPs are fundamentally different.

Gait Analysis and Motor Point Block in Dynamic Varus of the Rear Foot in a Head Injured Adult

This clinical note describes a typical case of dynamic varus deformity of the hind part of the foot in a head injured adult. Gait analysis objectified, by kinematic data, the perturbed movement of the rear foot in the frontal plane and identified, by dynamic electromyography, the overactive muscle (posterior tibialis) involved in the deformity. The diagnosis was confirmed by a motor point block of the posterior tibialis muscle with functional improvement. Kinematic data also showed improvement after the block. This case report illustrates the usefulness of gait analysis in diagnosis and management of gait disturbances in adult patients.

Influence des processus émotionnels automatiques sur la perception de la douleur

RésuméNos propos soutiennent une conception de la douleur en tant que produit final d’un processus perceptif complexe et global (le percept) au cours duquel le message nociceptif subit de nombreuses modulations centrales qui échappent à la conscience. En s’appuyant sur des exemples, nous verrons que, comme pour les autres modalités sensorielles, l’accès au stimulus qui déclenche la perception douloureuse, ainsi que le traitement de l’information dont celui-ci fait l’objet, sont influencés par de nombreux facteurs psychologiques (attentionnels, motivationnels, émotionnels, d’apprentissage, etc.). Nous étudierons, en particulier, l’impact des émotions sur la perception nociceptive. Une brève revue de la littérature sera complétée par des observations expérimentales originales qui traitent du cas particulier, encore mal connu, de l’influence des processus émotionnels inconscients sur le traitement de l’information nociceptive. Les expériences animales du conditionnement par la peur et les expériences humaines du conditionnent évaluatif, suggèrent que les caractéristiques affectives et sensorielles de la douleur pourrainent être encodées dans le système nerveux central d’une façon associative, non consciente et indélébile. Nos travaux ont montré que l’association répétée entre un stimulus nociceptif (le stimulus conditionné) et des stimulus inconditionnels (des images de valence émotionnelle positive ou négative), peut modifier la perception de ce stimulus nociceptif lorsqu’il est présenté ultérieurement dans un contexte émotionnellement neutre, et, que cet apprentissage est resté inconscient. En guise de conclusion, nous proposerons une définition des caractéristiques émotionnelles du système dédicacé au traitement de l’information nociceptive.SummaryThis review supports a conception of pain as the final outcome of a complex and global perceptive process (the percept) during which the nociceptive message is subjected to a large amount of central modulations escaping consciousness. Based on examples, we shall see that, as for other sensory modalities, access to the stimulus that triggers the painful percept, as wall as the processing of it, is influenced by a number of psychological factors (attention, motivation, emotion, learning, …). We shall examine, in particular, the impact of emotions on nociceptive perception. A brief review of the literature shall be extended by original experimental contributions, which concern the particular case, yet poorly understood, of the influence of unconscious emotional processes on the processing of nociceptive information. Animal experiments of fear conditioning and human experiments of evaluative conditioning suggest that the affective and sensorial characteristics of pain may be encoded in the central nervous system in a way that is associative, unconscious and indelible. Our experimental studies show that the repeated association between a nociceptive stimulus (the conditioned stimulus) and unconditioned stimuli (images of positive or negative emotional valence), may modify the perception of that nociceptive stimulus when it is presented subsequently in a neutral emotional context, and that this learning process remained unconscious. We shall conclude by proposing a definition of the emotional characteristics of the system dedicated to the processing of nociceptive information.