[Psychedelics in the field of chronic pain. A path to explore?] / Psychédéliques dans le domaine de la douleur chronique. Une piste à explorer?

Psychedelics are emerging as a therapeutic innovation in psychiatry and their use in chronic pain is worth exploring. In fact, they can modulate the serotonergic system, affecting central pain sensitization mechanisms. Ketamine, used for chronic analgesia, can lead to pain reduction, but additional studies are needed to assess its longterm effectiveness. "Classic" psychedelics are recently attracting renewed interest for their potential effects on chronic pain. Despite limited studies, evidence suggests analgesic benefits, an effect on inflammation, and potential impacts on certain functional disorders. These results pave the way for further research in this ever-evolving field.

Les psychédéliques émergent comme une innovation thérapeutique en psychiatrie et leur utilisation dans la douleur chronique mérite d'être explorée. En effet, ils peuvent moduler le système sérotoninergique, influençant les mécanismes de sensibilisation centrale à la douleur. La kétamine, utilisée en antalgie chronique, peut aboutir à une réduction de la douleur, mais des études supplémentaires sont nécessaires pour évaluer son efficacité à long terme. Les psychédéliques «classiques¼ suscitent un regain d'intérêt récent pour leurs effets potentiels sur la douleur chronique. Malgré des études limitées, des indices suggèrent des bénéfices analgésiques, une influence sur l'inflammation et des impacts potentiels sur certains troubles fonctionnels. Ces résultats ouvrent la voie à de nouvelles recherches dans ce domaine en constante évolution.

Downregulation of the schizophrenia risk-gene Dgcr2 alters early microcircuit development in the mouse medial prefrontal cortex.

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC. First, we demonstrate that Dgcr2 knock-down disrupts laminar positioning, dendritic morphology and excitatory activity of upper-layer PNs. Interestingly, inhibitory activity is also modified in Dgcr2 knock-down PNs, suggesting a broader microcircuit alteration involving interneurons. Further analyses show that the histological maturation of parvalbumin (PV) INs is not dramatically impaired, thus implying that other INs subtypes might be at play in the reported microcircuit alteration. Overall, this study unravels how local functional deficits of the early postnatal development of the mPFC can be induced by Dgcr2 knock-down in PNs.

[Personalized approach in chronic pain psychotherapy]. / Approche personnalisée dans la psychothérapie des douleurs chroniques.

Chronic pain is a complex phenomenon that includes three dimensions : biological, socio-cultural and psychological. The psychological aspect plays an amplifying role in the perception of pain and therefore, adjuvant psychotherapies are an important tool in the multidimensional management of chronic pain. In this article, we present the main psychotherapeutic approaches and techniques applied in the field of chronic pain which act on the cognitive-emotional, traumatic, as well as on the sensory level. The personalization of psychotherapeutic treatment, as well as the involvement of patients in its choice, should allow psychotherapeutic approaches to achieve their goal in terms of improving the quality of life of patients.

La douleur chronique est un phénomène complexe qui inclut trois dimensions : biologique, socioculturelle et psychologique. L'aspect psychologique joue un rôle amplificateur dans la perception douloureuse et de ce fait, les psychothérapies adjuvantes constituent un outil important quant à la prise en charge multidimensionnelle de la douleur chronique. Dans cet article, nous présentons les approches et techniques psychothérapeutiques principales appliquées dans le domaine de la douleur chronique qui agissent tant sur le plan cognitivo-émotionnel et traumatique que sur le plan sensoriel. La personnalisation du traitement psychothérapeutique ainsi que l'implication des patients dans son choix devraient permettre aux approches psychothérapeutiques d'atteindre leur objectif en termes d'amélioration de la qualité de vie des patients.

MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination.

The combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction remains unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the MCF2 gene in a boy with CBPS. Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse Mcf2 gene controls the embryonic migration of cortical projection neurons. Strikingly, we find that the CBPS-associated MCF2 mutation impairs cortical laminar positioning, supporting the hypothesis that alterations in the process of embryonic neuronal migration can lead to rare cases of CBPS.

The Candidate Schizophrenia Risk Gene DGCR2 Regulates Early Steps of Corticogenesis.

BACKGROUND: Alterations in early steps of cortical circuit assembly are thought to play a critical role in vulnerability to schizophrenia (SZ), but the pathogenic impact of SZ-risk mutations on corticogenesis remains to be determined. DiGeorge syndrome critical region 2 (DGCR2) is located in the 22q11.2 locus, whose deletion is a major risk factor for SZ. Moreover, exome sequencing of individuals with idiopathic SZ identified a rare missense mutation in DGCR2, further suggesting that DGCR2 is involved in SZ. METHODS: Here we investigated the function of Dgcr2 and the pathogenic impact of the SZ-risk DGCR2 mutation in mouse corticogenesis using in utero electroporation targeted to projection neurons. RESULTS: Dgcr2 knockdown impaired radial locomotion and final translocation of projection neurons, leading to persistent laminar positioning alterations. The DGCR2 missense SZ-risk mutation had a pathogenic impact on projection neuron laminar allocation by reducing protein expression. Mechanistically, we identified Dgcr2 as a novel member of the Reelin complex, regulating the phosphorylation of Reelin-dependent substrates and the expression of Reelin-dependent transcriptional targets. CONCLUSIONS: Overall, this study provides biological evidence that the SZ-risk gene DGCR2 regulates critical steps of early corticogenesis possibly through a Reelin-dependent mechanism. Additionally, we found that the SZ-risk mutation in DGCR2 has a pathogenic impact on cortical formation by reducing protein expression level, suggesting a functional role for DGCR2 haploinsufficiency in the 22q11.2 deletion syndrome.