La contribution des attentes à la régulation de la douleur

L’expérience de douleur et la réponse à son traitement sont teintées par les facteurs psychologiques, parmi lesquels figurent les attentes. Cette thèse propose de raffiner la compréhension de l’effet des attentes sur la régulation de la douleur par l’entremise de deux études quantitatives. D'abord, une étude expérimentale explore l'impact des attentes sur l'analgésie induite par contre-stimulation. Des volontaires sains ont été assignés à une condition contrôle ou à l’un des trois groupes au sein desquels les attentes étaient évaluées (attentes a priori) ou manipulées par l’entremise de suggestions (hyperalgésie ou analgésie). La douleur, l’anxiété et le réflexe nociceptif de flexion en réponse à des stimulations électriques ont été mesurés avant, pendant et après l’application d’un sac de glace. Les résultats suggèrent que les attentes a priori prédisent l’amplitude de l’analgésie, tandis que les attentes suggérées parviennent à potentialiser ou à bloquer les mécanismes endogènes d'inhibition de la douleur déclenchés par la contre-stimulation, indépendamment du niveau d’anxiété. Ensuite, une étude clinique se penche sur l'apport des attentes aux issues thérapeutiques de patients traités en centres multidisciplinaires de gestion de la douleur chronique. Préalablement au traitement, les attentes des patients quant aux résultats anticipés après six mois de traitement ont été évaluées. Les changements dans l’intensité douloureuse, les symptômes dépressifs, l’interférence de la douleur et la dramatisation face à la douleur, ainsi que l’impression de changement et la satisfaction face au traitement ont été évalués au suivi de six mois. Les résultats d'analyses de modélisation par équations structurelles appuient la relation prédictive entre les attentes et les issues thérapeutiques et soulignent l’impression de changement du patient comme variable médiatrice de cette association. En plus de se montrer supérieur à un modèle alternatif, ce modèle s'est avéré pertinent à travers différents sous-groupes. Dans l'ensemble, cette thèse contribue à démontrer le rôle déterminant des attentes dans le contexte de la douleur, tant au niveau physiologique que thérapeutique. Les conclusions qui se dégagent de cet ouvrage entraînent des retombées non négligeables et réitèrent la nécessité de considérer la perspective du patient afin d'optimiser les soins destinés au soulagement de la douleur.The experience of pain and response to pain treatments are influenced by psychological factors, such as expectations. This doctoral dissertation aims at refining the comprehension of the impact of expectations on pain regulation through two quantitative studies. First, an experimental study examined the impact of expectations on analgesia induced by heterotopic noxious counter-stimulation. Healthy volunteers were assigned to a control group or one of three experimental groups in which expectations were either assessed (a priori expectations) or manipulated using suggestions (hyperalgesia or analgesia). Acute shock-pain, shock-related anxiety and the nociceptive flexion reflex were measured in response to electrical stimulations before, during and after the application of a tonic cold pain. Results suggest that a priori expectations predict the magnitude of analgesia, while manipulated expectations either enhance or block counter-stimulation analgesia, independently of anxiety processes. Subsequently, a clinical study examined the association between expectations and clinical outcomes of chronic pain patients treated in multidisciplinary pain centers. Prior to their initial visit, patients' expected treatment outcomes were assessed. Six months after their initial visit, changes in pain intensity, depressive symptoms, pain interference and pain catastrophizing, along with satisfaction with treatment and impression of change were measured. Structural equations modeling analyses support the predictive association between expectations and all clinical outcomes as well as the mediating effect of patient’s impression of change. In addition to being superior to an alternative model, the proposed model was shown to be relevant across subgroups. Overall, this thesis contributes to the demonstration of the determinant role of expectations on physiological and therapeutic processes in the context of pain regulation. These findings reiterate the need to consider the patient's perspective and offer a valuable avenue towards the optimization of treatments intended at relieving pain

L'idéal de la raison dans la Critique de la raison pure d'Emmanuel Kant.

La raison, lieu des Idées, lieu du sens, recherche l’inconditionné. Cette exigence, considérée d’un point de vue théorique et telle que la conçoit Emmanuel Kant dans la Critique de la raison pure, est aussi source d’illusions lorsque la raison prétend que des objets correspondent à ses idées subjectives. La recherche de l’inconditionné s’accomplit, et trouve son aboutissement, dans l’idéal de la raison où se pose la question de Dieu. C’est à cette partie de la Critique de la raison pure, où Kant examine les prétentions théoriques de la théologie rationnelle, mais aussi sa signification pour la critique elle-même, que s’intéresse notre projet de mémoire

Pain catastrophizing and worry about health in generalized anxiety disorder

Because the diagnostic criteria of generalized anxiety disorder (GAD) are not tied to specific worry domains (worry is ‘generalized’), research on the content of worry in GAD is lacking. To our knowledge, no study has addressed vulnerability for specific worry topics in GAD. The goal of the current study, a secondary analysis of data from a clinical trial, is to explore the relationship between pain catastrophizing and worry about health in a sample of 60 adults with primary GAD. All data for this study were collected at pretest, prior to randomization to experimental condition in the larger trial. The hypotheses were that (1) pain catastrophizing would be positively related to the severity of GAD, (2) the relationship between pain catastrophizing and the severity of GAD would not be explained by intolerance of uncertainty and psychological rigidity, and (3) pain catastrophizing would be greater in participants reporting worry about health compared to those not reporting worry about health. All hypotheses were confirmed, suggesting that pain catastrophizing may be a threat-specific vulnerability for health-related worry in GAD. The implications of the current findings include a better understanding of the ideographic content of worry, which could help focus treatment interventions for individuals with GAD

Le sentiment d’appartenance à l’école : validation d’un modèle théorique prédisant l’engagement et le rendement scolaire en mathématiques d’élèves du secondaire = School belonging: validation of a theoretical model high school students’ engagement and academic achievement in mathematics

Résumé Au cours des dernières années, un certain nombre de théoriciens ont examiné le sentiment d’appartenance des élèves dans le contexte scolaire, afin de mieux comprendre sa relation positive avec le rendement scolaire. Pour approfondir la compréhension de ces processus psychologiques, nous avons appliqué le modèle d’Anderman et Freeman (2004) pour valider quatre hypothèses. L’échantillon comprend 2749 élèves du secondaire vivant au Québec. Nos résultats corroborent plusieurs éléments de ce modèle : d’abord, nos résultats appuient l’idée que l’appartenance à l’école constitue un élément fondamental est la base de l’engagement et de la réussite scolaire; deuxièmement, nos résultats renforcent le rôle important des émotions positives pour l’engagement des élèves. Abstract In recent years, a number of theorists have examined students’ sense of belonging in school contexts, in order to better understand the ways they can be connected to academic achievement. To more thoroughly investigate these psychological processes, we applied the Anderman and Freeman model (2004) to validate four hypotheses. The sample consists of 2749 high school students living in Quebec. Our results corroborate several elements of this model: first, our results support the idea that school belonging is the basis for academic engagement and achievement; second, our findings reinforce the important role of positive emotions for student engagement

The role of spatial frequencies for facial pain categorization

Studies on low-level visual information underlying pain categorization have led to inconsistent findings. Some show an advantage for low spatial frequency information (SFs) and others a preponderance of mid SFs. This study aims to clarify this gap in knowledge since these results have different theoretical and practical implications, such as how far away an observer can be in order to categorize pain. This study addresses this question by using two complementary methods: a data-driven method without a priori expectations about the most useful SFs for pain recognition and a more ecological method that simulates the distance of stimuli presentation. We reveal a broad range of important SFs for pain recognition starting from low to relatively high SFs and showed that performance is optimal in a short to medium distance (1.2–4.8 m) but declines significantly when mid SFs are no longer available. This study reconciles previous results that show an advantage of LSFs over HSFs when using arbitrary cutoffs, but above all reveal the prominent role of mid-SFs for pain recognition across two complementary experimental tasks

Muramyl Dipeptide Induces NOD2-Dependent Ly6Chigh Monocyte Recruitment to the Lungs and Protects Against Influenza Virus Infection

Bacterial peptidoglycan-derived muramyl dipeptide (MDP) and derivatives have long-recognized antiviral properties but their mechanism of action remains unclear. In recent years, the pattern-recognition receptor NOD2 has been shown to mediate innate responses to MDP. Here, we show that MDP treatment of mice infected with Influenza A virus (IAV) significantly reduces mortality, viral load and pulmonary inflammation in a NOD2-dependent manner. Importantly, the induction of type I interferon (IFN) and CCL2 chemokine was markedly increased in the lungs following MDP treatment and correlated with a NOD2-dependent enhancement in circulating monocytes. Mechanistically, the protective effect of MDP could be explained by the NOD2-dependent transient increase in recruitment of Ly6Chigh “inflammatory” monocytes and, to a lesser extent, neutrophils to the lungs. Indeed, impairment in both Ly6Chigh monocyte recruitment and survival observed in infected Nod2-/- mice treated with MDP was recapitulated in mice deficient for the chemokine receptor CCR2 required for CCL2-mediated Ly6Chigh monocyte migration from the bone marrow into the lungs. MDP-induced pulmonary monocyte recruitment occurred normally in IAV-infected and MDP-treated Ips-1-/- mice. However, IPS-1 was required for improved survival upon MDP treatment. Finally, mycobacterial N-glycolyl MDP was more potent than N-acetyl MDP expressed by most bacteria at reducing viral burden while both forms of MDP restored pulmonary function following IAV challenge. Overall, our work sheds light on the antiviral mechanism of a clinically relevant bacterial-derived compound and identifies the NOD2 pathway as a potential therapeutic target against IAV

Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

The CD81 Partner EWI-2wint Inhibits Hepatitis C Virus Entry

Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor