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.

Atypical influence of biomechanical knowledge in Complex Regional Pain Syndrome-towards a different perspective on body representation.

Part of the multifaceted pathophysiology of Complex Regional Pain Syndrome (CRPS) is ascribed to lateralized maladaptive neuroplasticity in sensorimotor cortices, corroborated by behavioral studies indicating that patients present difficulties in mentally representing their painful limb. Such difficulties are widely measured with hand laterality judgment tasks (HLT), which are also used in the rehabilitation of CRPS to activate motor imagery and restore the cortical representation of the painful limb. The potential of these tasks to elicit motor imagery is critical to their use in therapy, yet, the influence of the body's biomechanical constraints (BMC) on HLT reaction time, supposed to index motor imagery activation, is rarely verified. Here we investigated the influence of BMC on the perception of hand postures and movements in upper-limb CRPS. Patients were slower than controls in judging hand laterality, whether or not stimuli corresponded to their painful hand. Reaction time patterns reflecting BMC were mostly absent in CRPS and controls. A second experiment therefore directly investigated the influence of implicit knowledge of BMC on hand movement judgments. Participants judged the perceived path of movement between two depicted hand positions, with only one of two proposed paths that was biomechanically plausible. While the controls mostly chose the biomechanically plausible path, patients did not. These findings show non-lateralized body representation impairments in CRPS, possibly related to difficulties in using correct knowledge of the body's biomechanics. Importantly, they demonstrate the challenge of reliably measuring motor imagery with the HLT, which has important implications for the rehabilitation with these tasks.

No perceptual prioritization of non-nociceptive vibrotactile and visual stimuli presented on a sensitized body part.

High frequency electrical conditioning stimulation (HFS) is an experimental method to induce increased mechanical pinprick sensitivity in the unconditioned surrounding skin (secondary hyperalgesia). Secondary hyperalgesia is thought to be the result of central sensitization, i.e. increased responsiveness of nociceptive neurons in the central nervous system. Vibrotactile and visual stimuli presented in the area of secondary hyperalgesia also elicit enhanced brain responses, a finding that cannot be explained by central sensitization as it is currently defined. HFS may recruit attentional processes, which in turn affect the processing of all stimuli. In this study we have investigated whether HFS induces perceptual biases towards stimuli presented onto the sensitized arm by using Temporal Order Judgment (TOJ) tasks. In TOJ tasks, stimuli are presented in rapid succession on either arm, and participants have to indicate their perceived order. In case of a perceptual bias, the stimuli presented on the attended side are systematically reported as occurring first. Participants performed a tactile and a visual TOJ task before and after HFS. Analyses of participants' performance did not reveal any prioritization of the visual and tactile stimuli presented onto the sensitized arm. Our results provide therefore no evidence for a perceptual bias towards tactile and visual stimuli presented onto the sensitized arm.

Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies.

Several studies have used neuroimaging techniques to investigate brain correlates of the attentional modulation of pain. Although these studies have advanced the knowledge in the field, important confounding factors such as imprecise theoretical definitions of attention, incomplete operationalization of the construct under exam, and limitations of techniques relying on measuring regional changes in cerebral blood flow have hampered the potential relevance of the conclusions. Here, we first provide an overview of the major theories of attention and of attention in the study of pain to bridge theory and experimental results. We conclude that load and motivational/affective theories are particularly relevant to study the attentional modulation of pain and should be carefully integrated in functional neuroimaging studies. Then, we summarize previous findings and discuss the possible neural correlates of the attentional modulation of pain. We discuss whether classical functional neuroimaging techniques are suitable to measure the effect of a fluctuating process like attention, and in which circumstances functional neuroimaging can be reliably used to measure the attentional modulation of pain. Finally, we argue that the analysis of brain networks and spontaneous oscillations may be a crucial future development in the study of attentional modulation of pain, and why the interplay between attention and pain, as examined so far, may rely on neural mechanisms shared with other sensory modalities.

Prisms for pain. Can visuo-motor rehabilitation strategies alleviate chronic pain?

BACKGROUND AND AIMS: Prism adaptation (PA) is a non-invasive procedure in which participants perform a visuo-motor pointing task while wearing prism goggles inducing a lateral displacement of the visual field and a mismatch between the seen and felt position of the pointing hand. PA is thought to induce a reorganization of sensorimotor coordination, and has been used successfully to rehabilitate neglect following right-hemisphere lesions. Because studies have shown that complex regional pain syndrome (CRPS) is associated with neglect-like symptoms, it was proposed that PA could be used to alleviate pain in these patients. DATABASE: A search for peer-reviewed articles on neglect-like symptoms in CRPS and on the use of prisms in CRPS was conducted using the PubMed database. RESULTS: There is still no agreement as to whether CRPS patients really present neglect symptoms and, if they do, what it is that they neglect. Furthermore, there is insufficient data to determine whether PA exerts an effect on CRPS symptoms. Finally, it remains unknown whether neglect can be observed in other types of lateralized pain, or whether PA could be useful for these patients. CONCLUSION: By highlighting open issues, our review provides guidelines for future studies on the use of prisms in pain. The assessment of neglect in patients with CRPS as well as other types of lateralized chronic pain should be characterized using a combination of neuropsychological methods assessing the multiple aspects of neglect in a more refined manner. In addition, further studies should investigate the mechanisms through which PA may modulate pain.

Solitary Langerhans cell histiocytoma.

Biopsy of a solitary tumor of the buttock in a 3-month-old girl was diagnosed as a histiocytic proliferation suggestive of histiocytosis X. Electron microscopy showed Birbeck granules and dense myelinlike bodies within the cytoplasm of the tumor cells. An immunoperoxidase study, using a panel of monoclonal antibodies (OKT6, OKT4, and OKM1) and a polyclonal anti-S100 protein antibody, showed positive staining for OKT6 and OM1 and moderately positive staining for OKT4 and S100. After surgery to remove the tumor, visceral involvement could not be demonstrated during a 20-month follow-up.

Intra- and inter-individual variations in cornified envelope peptide composition in normal and psoriatic skin.

Cornified envelopes from the stratum corneum of healthy volunteers and from the involved and uninvolved skin of psoriatic patients were electrophoretically purified, and their peptide composition analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) after cyanogen bromide cleavage. The resulting envelope peptide patterns (EPPs) were compared. In normal subjects, mainly quantitative minor differences in the EPPs were observed between different individuals. In the same individual, palms and soles could be distinguished from other body sites by their EPPs. The palm and sole samples presented identical patterns which were different from the patterns found with samples from other body sites. In psoriatic patients, EPPs of uninvolved skin resembled closely those of healthy epidermis, but showed striking differences from those of lesional skin. The EPPs of psoriatic lesional skin showed a characteristic accumulation of small peptides with molecular weights of 3-11 kDa. The EPP of lesional skin returned to normal during PUVA therapy, indicating that the changes in the biochemical composition of the cornified envelope are correlated with the clinical status of the disease.

[Clinical and pathophysiological contribution of event-related potentials used to study migraine headache]. / Intérêts clinique et physiopathologique des potentiels évoqués cognitifs dans la migraine.

Event-related potentials are electric brain manifestations evoked by mental activities. This neurophysiological technique is able to describe temporal succession of cognitive processing and allows to measure the neurobiological correlates of each cognitive activity. The evoked potentials of the oddball paradigm and the Contingent Negative Variation (CNV) are also concerned by clinical applications in neuropsychiatry, in neurology and in psychopharmacology. In the case of migraine, the studies with CNV recorded between migraine attacks are characterized by two major phenomena, cerebral hyperreactivity and lack of habituation to repetitive stimuli. From cognitive point of view, this can be interpreted as a difficulty from migraine sufferers to adapt their information-processing to environmental constraints. From neurological point of view, this trouble is related with dysregulation of norepinephrin and serotonin ascending pathways. Studies with the oddball paradigm potentials remain non consistent. The mismatch between different methodologies could explain such a lack of consistency. The neurophysiological studies have contributed to new physiopathological hypothesis of migraine. Those hypothesis reveal that a shift in the brain metabolic homeostasis could be the common factor of migraine attacks. The clinical contribution of event-related potentials is of little use in the diagnosis of migraine. But two purposes have been suggested: the differential diagnosis between common migraine and tension-type headaches and the monitoring of beta-blocking agents prophylaxis.

[Diffuse cutaneous mastocytosis without permanent lesion]. / Mastocytose cutanée diffuse sans lésion permanente.

Cutaneous mastocytosis usually includes objective skin signs such as pigmented maculopapulae or skin infiltration. We report an unusual case of cutaneous mastocytosis without systemic involvement in a 9-month old infant. Clinical expression was entirely functional (pruritus, urticaria) with no permanent lesions. There were 22 times more mastocytes found in the skin biopsy than in similar biopsies obtained in healthy control subjects of the same age, which corresponds to the counts found in cutaneous mastocytosis. Diffuse cutaneous mastocytosis with no permanent lesions is an exceptional form of mastocytosis (3 cases reported in the literature). The long-term outcome is unknown. This syndrome should be distinguished from idiopathic anaphylaxis by quantification of the dermal mastocytes.

[Comparative study of efficacy and effect on plasma cortisol levels of micronised desonide cream 0.1 p. 100 versus betamethasone dipropionate cream 0.05 p. 100 In the treatment of childhood atopic dermatitis]. / Etude comparative de l'efficacité et du retentissement systémique du désonide micronisé crème 0,1 p. 100 et du diproprionate de bétaméthasone crème 0.05 p. 100 dans le traitement de la dermatite atopique de l'enfant.

OBJECTIVE: Systemic side effects of local corticosteroid therapy may occur when treating chronic inflammatory dermatoses in children. We compared the effect of micronized desonide cream 0.1 p.100 versus betamethasone dipropionate cream 0.5 p.100. PATIENTS AND METHODS: A randomized double-blind trial was conducted to assess the efficacy of micronized desonide cream 0.1 p.100 (group 1) versus bethamethasone cream dipropionate 0.05 p.100 (group 2) in children treated for atopic dermatitis and to compare their effects on serum cortisol levels 8 hours after administration. Twenty-nine patients, mean age 13.8 months were included (15 in group 1 and 14 in group 2). The creams were applied twice a day from day 1 to 5 then once a day from day 6 to 7 and finally once every two days to day 15. RESULTS: The two treatments were effective with a decrease in body surface area involved and an improvement in lesion score from day 5 to day 20. Cortisolemia fell off significantly for both treatments between day 0 and day 5 (group 1: Deltad5=-4.74 mg/ml, p=0.01; group 2: Deltad5=-13.06 mg/ml, p<0.0001), only for group 2 between day 0 and day 20 (Deltad20=-7.38 mg/ml, p=0.02) and to a lesser degree between day 0 and day 30 (Deltad30=-3.18 mg/ml, p=0.06). The decrease was greater in group 2 than in group 1 on day 5 (p=0.01) and to a lesser degree at day 20 (p=0.06). CONCLUSIONS: Micronized desonide cream 0.1 p.100 has less potential for suppressing the adrenal cortisol axis than betamethasone dipropionate cream 0.05 p.100 while the therapeutic effect on childhood atopic dermatitis is the same.

[Treatment of psoriasis by oral calcitriol. A study of 5 cases and review of the literature]. / Traitement du psoriasis par le calcitriol per os. Etude de cinq observations et revue de la littérature.

Vitamin D topical analogues are now considered an excellent adjunct to the therapy of psoriasis. Systemic vitamin D3 treatment has been used occasionally, especially in case of associated hypocalcemia. We report five patients (aged 6, 16, 36, 58 and 79 years) successfully treated with vitamin D3 per os. Four had erythrodermic and/or pustulous psoriasis, and two of these had concomitant hypocalcemia. The fifth patient was a girl with pseudohypoparathyroidism and psoriasis vulgaris. The association of hypocalcemia and severe psoriasis is classical and was an incentive to try vitamin D treatment. A review of the literature showed that vitamin D can also be reported as a treatment of psoriasis vulgaris. Hypercalciuria and hypercalcemia are limiting risks. However calcium toxicity seems to be minor when vitamin D is given once a day at bedtime in doses lower than 2 micrograms/24 h. Double blind studies should be performed to determine the real efficacy of this treatment.

[Epidemiology of urticaria in infants]. / Epidémiologie de l'urticaire chez l'enfant.

Epidemiology of childhood urticaria and especially that of infants is badly understood because of a lack of studies devoted to this age group. A retrospective study of 40 infants that were hospitalised for urticaria has been made to clarify the factors that produce urticaria at that age. Certain clinical signs seem to be more frequent at this age, such as the bruised appearance of the lesions. Acute urticaria is the most frequent form. An etiology has been confirmed or suspected in 2/3 cases: intolerance of cow milk proteins before 6 months, drug and infection causes after 6 months. Prospective studies of infantile urticaria are necessary.

Keeping pain out of your mind: the role of attentional set in pain.

BACKGROUND: The involuntary capture of attention by pain may, to some extent, be controlled by psychological variables. In this paper, we investigated the effect of attentional set (i.e., the collection of task-related features that a person is monitoring in order to successfully pursue a goal) on pain. METHODS: Two experiments are reported in which the task relevance of the modality and spatial location of a target stimulus was manipulated. In both experiments, somatosensory and auditory stimuli were presented on each trial. In experiment 1, 29 participants were cued on each trial to localize either a somatosensory or an auditory target. In experiment 2, 37 participants were cued on each trial to identify either a somatosensory or an auditory target at a particular location. RESULTS: In experiment 1, self-reported pain intensity and unpleasantness were reduced when participants had to localize the auditory target. The location of the painful stimulus relative to the location of the auditory target did not affect pain. In experiment 2, again, pain intensity and unpleasantness ratings were reduced when participants identified the auditory target. Now, the location of the painful stimulus relative to the location of the auditory target moderated the effect. Pain intensity was less when the painful stimulus was at a different location than the auditory target. CONCLUSIONS: Results are discussed in terms of the attentional set hypothesis, and we argue that the effectiveness of distraction tasks depends on the degree to which the task-relevant features of the distraction task are distinct from pain-related features.

Steady-state evoked potentials to study the processing of tactile and nociceptive somatosensory input in the human brain.

The periodic presentation of a sensory stimulus induces, at certain frequencies of stimulation, a sustained electroencephalographic response of corresponding frequency, known as steady-state evoked potentials (SS-EP). In visual, auditory and vibrotactile modalities, studies have shown that SS-EP reflect mainly activity originating from early, modality-specific sensory cortices. Furthermore, it has been shown that SS-EP have several advantages over the recording of transient event-related brain potentials (ERP), such as a high signal-to-noise ratio, a shorter time to obtain reliable signals, and the capacity to frequency-tag the cortical activity elicited by concurrently presented sensory stimuli. Recently, we showed that SS-EP can be elicited by the selective activation of skin nociceptors and that nociceptive SS-EP reflect the activity of a population of neurons that is spatially distinct from the somatotopically-organized population of neurons underlying vibrotactile SS-EP. Hence, the recording of SS-EP offers a unique opportunity to study the cortical representation of nociception and touch in humans, and to explore their potential crossmodal interactions. Here, (1) we review available methods to achieve the rapid periodic stimulation of somatosensory afferents required to elicit SS-EP, (2) review previous studies that have characterized vibrotactile and nociceptive SS-EP, (3) discuss the nature of the recorded signals and their relationship with transient event-related potentials and (4) outline future perspectives and potential clinical applications of this technique.

Cognitive aspects of nociception and pain: bridging neurophysiology with cognitive psychology.

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.

Autonomic pain responses during sleep: a study of heart rate variability.

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance.

Laser evoked responses to painful stimulation persist during sleep and predict subsequent arousals.

We studied behavioural responses and 32-channel brain potentials to nociceptive stimuli during all-night sleep in 12 healthy subjects, using sequences of thermal laser pulses delivered over the dorsum of the hand. Laser stimuli less than 20 dB over perception threshold had clear awakening properties, in accordance with the intrinsic threatening value of nociceptive signals. Even in cases where nociceptive stimulation did not interrupt sleep, it triggered motor responses in 11% of trials. Only four subjects reported dreams, and on morning questionnaires there was no evidence of incorporation to dreams of nociceptive stimuli. Contrary to previous reports suggesting the absence of cortical nociceptive responses during sleep, we were able to record brain-evoked potentials to laser (LEPs) during all sleep stages. Sleep LEPs were in general attenuated, but their morphology was sleep-stage-dependent: in stage 2, the weakened initial response was often followed by a high-amplitude negative wave with typical features of a K-complex. During paradoxical sleep (PS) LEP morphology was similar to that of waking, but frontal components showed strong attenuation, consistent with the reported frontal metabolic deactivation. A late positive component (450-650 ms) was recorded in both stage 2 and PS, the amplitude of which was significantly enhanced in trials that were followed by an arousal. This response appeared functionally related to the P3 wave, which in waking subjects has been associated to conscious perception and memory encoding.

Urticaria in infants: a study of forty patients.

A retrospective study was carried out in 40 infants, age 1 to 24 months, with urticaria. Acute urticaria was seen most frequently (85%), followed by recurrent (10%) and chronic disease (5%). Several clinical features such as frequency of angioedema and hemorrhagic lesions appeared to be specific to urticaria in infants. An underlying cause was identified or suspected in 65% of cases: foods in 25%, and drugs and infections in 37.5%. Under 6 months of age, all infants had acute urticaria and 75% had cow's milk allergy. After 6 months of age, the main causes were drug intake (mostly aspirin and amoxicillin) and/or infections (mainly viral) (50%). Atopy was not overrepresented (20%), although a possible link between atopy and recurrent urticaria was noted. After a follow-up of 2 to 7.5 years, 96% of patients were symptom free. Thus, our results indicate that clinical and etiologic features of urticaria in infants are somewhat different from those of adults and children.