Multicenter assessment of quantitative sensory testing (QST) for the detection of neuropathic-like pain responses using the topical capsaicin model.

BACKGROUND: The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers. AIM: The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers. METHODS: A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic. RESULTS: Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain (P < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT. CONCLUSION: These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses.

Contexte: L'utilisation de tests sensoriels quantitatifs (QST) dans les études multicentriques est limitée, en partie à cause de l'absence de procédures normalisées au sein des centres.But: évaluer l'application du modèle de la douleur traitée par capsaïcine en tant que modèle expérimental humain de substitution pour la douleur neuropathique dans différents centres et vérifier les variations dans les mesures des tests sensoriels quantitatifs entre les centres.Méthodes: Une étude multicentrique menée par le Réseau québécois de recherche sur la douleur dans six laboratoires a permis d'évaluer neuf paramètres de tests sensoriels quantitatifs chez 60 sujets en bonne santé traités par capsaïcine topique afin de modéliser la douleur unilatérale et l'allodynie. Les mêmes mesures (sans capsaïcine) ont été prises chez 20 patients atteints de douleur neuropathique chronique recrutés dans une clinique de la douleur indépendante.Résultats: Les résultats ont révélé une différence significative entre la zone de peau traitée à la capsaïcine et la zone contrôle pour six paramètres : 1) le seuil de détection du froid (CTF) et 2) le seuil de perception de la douleur causée par le froid (CPT) étaient plus bas sur le côté traité par capsaïcine chez les sujets en bonne santé, ce qui indique une diminution de la sensibilité au froid, 3) Le seuil de perception de la douleur causée par la chaleur (HPT) était plus bas sur le côté traité par capsaïcine chez les sujets en bonne santé, ce qui suggère une augmentation de la sensibilité à la douleur causée par la chaleur; 4) l'allodynie mécanique dynamique (DMA), 5) la douleur mécanique après deux stimulations (MPS2) et 6) la somme de la douleur mécanique après 10 stimulations (MPS10) ont augmenté sur le côté traité à la capsaïne, ce qui suggère une augmentation de la douleur mécanique (p < 0,002). Le CDT, le CPT et le HPT ont démontré des effets comparables dans les six centres, le CPT et le HPT démontrant la meilleure sensibilité. Les données des patients ont révélé une différence significative entre le côté affecté et le non côté non affecté, mais seulement dans le cas du CDT.Conclusion: Ces résultats soutiennent l'application de tests sensoriels quantitatifs dans les études multicentriques portant sur les réponses normales et pathologiques à la douleur.

Empathy in paediatric intensive care nurses part 1: Behavioural and psychological correlates.

AIM: To determine if differences exist between paediatric intensive care nurses and allied health professionals in empathy, secondary trauma, burnout, pain exposure and pain ratings of self and others. Early and late career differences were also examined. BACKGROUND: Nurses are routinely exposed to patient pain expression. This work context may make them vulnerable to adverse outcomes such as desensitization to patient pain or a compromise in personal well-being. DESIGN: Cross-sectional study. METHODS: Data were collected from a convenience sample of paediatric intensive care nurses (n = 27) and allied health professionals (n = 24), from September 2014-June 2015, at a Canadian health centre. Both groups completed one demographic and three behavioural scales. Participants underwent fMRI while rating the pain of infant and adult patients in a series of video clips. Data were analyzed using parametric and non-parametric methods. fMRI results are reported in a second paper. RESULTS: Nurses were significantly more likely to be exposed to pain at work than allied health professionals and scored significantly higher on dimensions of empathy, secondary trauma and burnout. Nurses scored their own pain and the pain of infant and adult patients, higher than allied health participants. Less experienced nurses had higher secondary trauma and burnout scores than more experienced nurses. CONCLUSIONS: Paediatric intensive care work demands, such as patient pain exposure, may be associated with nurse's higher report of empathy and pain in self and others, but also with higher levels of secondary trauma and burnout, when compared with allied health professionals.

Empathy in paediatric intensive care nurses part 2: Neural correlates.

AIMS: To determine if there are brain activity differences between paediatric intensive care nurses and allied health professionals during pain intensity rating tasks and test whether these differences are related to the population observed (infant or adult) and professional experience. BACKGROUND: The underestimation of patients' pain by healthcare professionals has generally been associated with patterns of change in neural response to vicarious pain, notably reduced activation in regions associated with affective sharing and increased activation in regions associated with regulation, compared with controls. Paediatric nurses, however, have recently been found to provide higher estimates of infants' pain in comparison to allied health controls, suggesting that changes in neural response of this population might be different than other health professionals. DESIGN: Cross-sectional study. METHODS: Functional MRI data were acquired from September 2014-June 2015 and used to compare changes in brain activity in 27 female paediatric care nurses and 24 allied health professionals while rating the pain of infants and adults in a series of video clips. RESULTS: Paediatric nurses rated infant and adult pain higher than allied health professionals, but the two groups' neural response only differed during observation of infant pain; paediatric nurses mainly showed significantly less activation in the medial prefrontal cortex (linked to cognitive empathy) and in the left anterior insula and inferior frontal cortex (linked to affective sharing). CONCLUSIONS: Patterns of neural activity to vicarious pain may vary across healthcare professions and patient populations and the amount of professional experience might explain part of these differences.

BDNF Val66Met Polymorphism Influences Visuomotor Associative Learning and the Sensitivity to Action Observation.

Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system.

EEVEE: the Empathy-Enhancing Virtual Evolving Environment.

Empathy is a multifaceted emotional and mental faculty that is often found to be affected in a great number of psychopathologies, such as schizophrenia, yet it remains very difficult to measure in an ecological context. The challenge stems partly from the complexity and fluidity of this social process, but also from its covert nature. One powerful tool to enhance experimental control over such dynamic social interactions has been the use of avatars in virtual reality (VR); information about an individual in such an interaction can be collected through the analysis of his or her neurophysiological and behavioral responses. We have developed a unique platform, the Empathy-Enhancing Virtual Evolving Environment (EEVEE), which is built around three main components: (1) different avatars capable of expressing feelings and emotions at various levels based on the Facial Action Coding System (FACS); (2) systems for measuring the physiological responses of the observer (heart and respiration rate, skin conductance, gaze and eye movements, facial expression); and (3) a multimodal interface linking the avatar's behavior to the observer's neurophysiological response. In this article, we provide a detailed description of the components of this innovative platform and validation data from the first phases of development. Our data show that healthy adults can discriminate different negative emotions, including pain, expressed by avatars at varying intensities. We also provide evidence that masking part of an avatar's face (top or bottom half) does not prevent the detection of different levels of pain. This innovative and flexible platform provides a unique tool to study and even modulate empathy in a comprehensive and ecological manner in various populations, notably individuals suffering from neurological or psychiatric disorders.

Feeling but not caring: empathic alteration in narcissistic men with high psychopathic traits.

Psychopathy is a personality disorder characterized by specific interpersonal-affective deficits and social deviance often marked by reduced empathy and decreased affective response to the suffering of others. However, recent findings in community samples suggest that the somatosensory resonance to other's pain measured with electroencephalography (EEG) is increased by psychopathic traits. This study aimed at comparing both the response to physical pain and the observation of pain being inflicted to another person in individuals with clinically significant psychopathic traits, namely patients with severe narcissistic personality disorder (NPD, n=11), and community controls (CC, n=13). The gating of somatosensory responses to a tactile steady-state stimulation (25 Hz) during the observation of pain-evoking and non-painful visual stimuli of hands was measured using EEG. Pain thresholds were assessed with a quantitative sensory testing (QST) battery. NPD compared with CC subjects showed similar thermal pain thresholds, but significantly higher pain pressure thresholds (PPT). Significantly greater somatosensory gating (SG) during the anticipation and the observation of pain in others was observed in NPD compared with CC subjects, but this difference was not associated with differences in self-pain perception. SG to pain observation was positively correlated with the Impulsivity-Egocentricity (IE) dimension of psychopathy. These findings demonstrated a stronger somatosensory resonance in the high psychopathic trait NPD group that suggests an increased somatic representation of observed pain despite lower dispositional empathy.

The influence of visual perspective on the somatosensory steady-state response during pain observation.

The observation and evaluation of other's pain activate part of the neuronal network involved in the actual experience of pain, including those regions subserving the sensori-discriminative dimension of pain. This was largely interpreted as evidence showing that part of the painful experience can be shared vicariously. Here, we investigated the effect of the visual perspective from which other people's pain is seen on the cortical response to continuous 25 Hz non-painful somatosensory stimulation (somatosensory steady-state response: SSSR). Based on the shared representation framework, we expected first-person visual perspective (1PP) to yield more changes in cortical activity than third-person visual perspective (3PP) during pain observation. Twenty healthy adults were instructed to rate a series of pseudo-dynamic pictures depicting hands in either painful or non-painful scenarios, presented either in 1PP (0-45° angle) or 3PP (180° angle), while changes in brain activity was measured with a 128-electode EEG system. The ratings demonstrated that the same scenarios were rated on average as more painful when observed from the 1PP than from the 3PP. As expected from previous works, the SSSR response was decreased after stimulus onset over the left caudal part of the parieto-central cortex, contralateral to the stimulation side. Moreover, the difference between the SSSR was of greater amplitude when the painful situations were presented from the 1PP compared to the 3PP. Together, these results suggest that a visuospatial congruence between the viewer and the observed scenarios is associated with both a higher subjective evaluation of pain and an increased modulation in the somatosensory representation of observed pain. These findings are discussed with regards to the potential role of visual perspective in pain communication and empathy.

The modulation of somatosensory resonance by psychopathic traits and empathy.

A large number of neuroimaging studies have shown neural overlaps between first-hand experiences of pain and the perception of pain in others. This shared neural representation of vicarious pain is thought to involve both affective and sensorimotor systems. A number of individual factors are thought to modulate the cerebral response to other's pain. The goal of this study was to investigate the impact of psychopathic traits on the relation between sensorimotor resonance to other's pain and self-reported empathy. Our group has previously shown that a steady-state response to non-painful stimulation is modulated by the observation of other people's bodily pain. This change in somatosensory response was interpreted as a form of somatosensory gating (SG). Here, using the same technique, SG was compared between two groups of 15 young adult males: one scoring very high on a self-reported measure of psychopathic traits [60.8 ± 4.98; Levenson's Self-Report Psychopathy Scale (LSRP)] and one scoring very low (42.7 ± 2.94). The results showed a significantly greater reduction of SG to pain observation for the high psychopathic traits group compared to the low psychopathic traits group. SG to pain observation was positively correlated with affective and interpersonal facet of psychopathy in the whole sample. The high psychopathic traits group also reported lower empathic concern (EC) scores than the low psychopathic traits group. Importantly, primary psychopathy, as assessed by the LSRP, mediated the relation between EC and SG to pain observation. Together, these results suggest that increase somatosensory resonance to other's pain is not exclusively explained by trait empathy and may be linked to other personality dimensions, such as psychopathic traits.

The neural network of motor imagery: an ALE meta-analysis.

Motor imagery (MI) or the mental simulation of action is now increasingly being studied using neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging. The booming interest in capturing the neural underpinning of MI has provided a large amount of data which until now have never been quantitatively summarized. The aim of this activation likelihood estimation (ALE) meta-analysis was to provide a map of the brain structures involved in MI. Combining the data from 75 papers revealed that MI consistently recruits a large fronto-parietal network in addition to subcortical and cerebellar regions. Although the primary motor cortex was not shown to be consistently activated, the MI network includes several regions which are known to play a role during actual motor execution. The body part involved in the movements, the modality of MI and the nature of the MI tasks used all seem to influence the consistency of activation within the general MI network. In addition to providing the first quantitative cortical map of MI, we highlight methodological issues that should be addressed in future research.

Modulation of brain activity during action observation: influence of perspective, transitivity and meaningfulness.

The coupling process between observed and performed actions is thought to be performed by a fronto-parietal perception-action system including regions of the inferior frontal gyrus and the inferior parietal lobule. When investigating the influence of the movements' characteristics on this process, most research on action observation has focused on only one particular variable even though the type of movements we observe can vary on several levels. By manipulating the visual perspective, transitivity and meaningfulness of observed movements in a functional magnetic resonance imaging study we aimed at investigating how the type of movements and the visual perspective can modulate brain activity during action observation in healthy individuals. Importantly, we used an active observation task where participants had to subsequently execute or imagine the observed movements. Our results show that the fronto-parietal regions of the perception action system were mostly recruited during the observation of meaningless actions while visual perspective had little influence on the activity within the perception-action system. Simultaneous investigation of several sources of modulation during active action observation is probably an approach that could lead to a greater ecological comprehension of this important sensorimotor process.

Decreasing phantom limb pain through observation of action and imagery: a case series.

BACKGROUND: Phantom limb pain is often resistant to treatment. Techniques based on visual-kinesthetic feedback could help reduce it. OBJECTIVE: The objective of the current study was to test if a novel intervention combining observation and imagination of movements can reduce phantom limb pain. METHODS: This single-case multiple baseline study included six persons with upper or lower limb phantom pain. Participants' pain and imagery abilities were assessed by questionnaires. After a 3-5-week baseline, participants received a two-step intervention of 8 weeks. Intervention 1 was conducted at the laboratory with a therapist (two sessions/week) and at home (three sessions/week); and Intervention 2 was conducted at home only (five times/week). Interventions combined observation and imagination of missing limb movements. Participants rated their pain level and their ease to imagine daily throughout the study. RESULTS: Time series analyses showed that three participants rated their pain gradually and significantly lower during Intervention 1. During Intervention 2, additional changes in pain slopes were not significant. Four participants reported a reduction of pain greater than 30% from baseline to the end of Intervention 2, and only one maintained his gains after 6 months. Group analyses confirmed that average pain levels were lower after intervention than at baseline and had returned to baseline after 6 months. Social support, degree of functionality, and perception of control about their lives prior to the intervention correlated significantly with pain reduction. CONCLUSIONS: Persons with phantom limb pain may benefit from this novel intervention combining observation and motor imagery. Additional studies are needed to confirm our findings, elucidate mechanisms, and identify patients likely to respond.