L'ocytocine, peptide aux multiples facettes

Accouchement, naissance, attachement parents-enfant : quiconque s’y intéresse a entendu parler de cette molécule à tout faire, l’ocytocine, surnommée hormone de l’amour. Invitation est faite à découvrir ce petit peptide

The oxytocinergic descending control of pain and its modulation by neonatal maternal separation

L’ocytocine est un petit peptide synthétisé par des neurones de l’hypothalamus. Il est connu pour ses rôles dans la reproduction et les interactions sociales, en particulier dans les interactions mère-enfants, mais possède également un effet analgésique endogène. Au cours de cette thèse, j’ai cherché à comprendre plus en détail les circuits qui sous-tendent son effet analgésique. Dans un second temps j’ai cherché à déterminer si une séparation maternelle précoce, qui affecte les interactions mère-enfants, perturbe les réponses à la douleur et l’analgésie ocytocinergique chez la descendance. Ces travaux ont permis d’identifier un groupe de neurones ocytocinergiques dans l’hypothalamus, capables de diminuer la douleur par une double action. D’une part ils inhibent directement la transmission de l’information nociceptive dans la moelle épinière, et d’autre part contrôlent l’activité de neurones à ocytocine libérant la molécule dans la circulation sanguine. Notre étude sur la séparation maternelle démontre qu’elle induit une hypersensibilité à la douleur à l’âge adulte et un dysfonctionnement de l’analgésie endogène ocytocinergique.Oxytocin is a small peptide synthesized in hypothalamic neurons. She is well known for its roles in reproduction and social interactions, especially in mother-infant interactions, but also displays analgesic effects. During this thesis, I tried to get a better understanding of the circuits underlying OT analgesia. Then, I tried to determine if neonatal maternal separation, affecting mother-infant interactions, alters adult pain responses and oxytocin analgesia. This work allowed to identify a subgroup of oxytocinergic neurons in the hypothalamus, able to decrease pain through a dual action. They directly inhibit nociceptive transmission in the spinal cord and control the activity of another population of oxytocinergic neurons releasing the peptide in the bloodstream. Our work on maternal separation shows that it induces nociceptive hypersensitivity at adulthood, and a dysfunction in oxytocin analgesia

The oxytocinergic descending control of pain and its modulation by neonatal maternal separation

L’ocytocine est un petit peptide synthétisé par des neurones de l’hypothalamus. Il est connu pour ses rôles dans la reproduction et les interactions sociales, en particulier dans les interactions mère-enfants, mais possède également un effet analgésique endogène. Au cours de cette thèse, j’ai cherché à comprendre plus en détail les circuits qui sous-tendent son effet analgésique. Dans un second temps j’ai cherché à déterminer si une séparation maternelle précoce, qui affecte les interactions mère-enfants, perturbe les réponses à la douleur et l’analgésie ocytocinergique chez la descendance. Ces travaux ont permis d’identifier un groupe de neurones ocytocinergiques dans l’hypothalamus, capables de diminuer la douleur par une double action. D’une part ils inhibent directement la transmission de l’information nociceptive dans la moelle épinière, et d’autre part contrôlent l’activité de neurones à ocytocine libérant la molécule dans la circulation sanguine. Notre étude sur la séparation maternelle démontre qu’elle induit une hypersensibilité à la douleur à l’âge adulte et un dysfonctionnement de l’analgésie endogène ocytocinergique.Oxytocin is a small peptide synthesized in hypothalamic neurons. She is well known for its roles in reproduction and social interactions, especially in mother-infant interactions, but also displays analgesic effects. During this thesis, I tried to get a better understanding of the circuits underlying OT analgesia. Then, I tried to determine if neonatal maternal separation, affecting mother-infant interactions, alters adult pain responses and oxytocin analgesia. This work allowed to identify a subgroup of oxytocinergic neurons in the hypothalamus, able to decrease pain through a dual action. They directly inhibit nociceptive transmission in the spinal cord and control the activity of another population of oxytocinergic neurons releasing the peptide in the bloodstream. Our work on maternal separation shows that it induces nociceptive hypersensitivity at adulthood, and a dysfunction in oxytocin analgesia

Caractérisation du contrôle descendant inhibiteur ocytocinergique et de sa modulation par un stress de séparation maternelle néonatale

Oxytocin is a small peptide synthesized in hypothalamic neurons. She is well known for its roles in reproduction and social interactions, especially in mother-infant interactions, but also displays analgesic effects. During this thesis, I tried to get a better understanding of the circuits underlying OT analgesia. Then, I tried to determine if neonatal maternal separation, affecting mother-infant interactions, alters adult pain responses and oxytocin analgesia. This work allowed to identify a subgroup of oxytocinergic neurons in the hypothalamus, able to decrease pain through a dual action. They directly inhibit nociceptive transmission in the spinal cord and control the activity of another population of oxytocinergic neurons releasing the peptide in the bloodstream. Our work on maternal separation shows that it induces nociceptive hypersensitivity at adulthood, and a dysfunction in oxytocin analgesia.L’ocytocine est un petit peptide synthétisé par des neurones de l’hypothalamus. Il est connu pour ses rôles dans la reproduction et les interactions sociales, en particulier dans les interactions mère-enfants, mais possède également un effet analgésique endogène. Au cours de cette thèse, j’ai cherché à comprendre plus en détail les circuits qui sous-tendent son effet analgésique. Dans un second temps j’ai cherché à déterminer si une séparation maternelle précoce, qui affecte les interactions mère-enfants, perturbe les réponses à la douleur et l’analgésie ocytocinergique chez la descendance. Ces travaux ont permis d’identifier un groupe de neurones ocytocinergiques dans l’hypothalamus, capables de diminuer la douleur par une double action. D’une part ils inhibent directement la transmission de l’information nociceptive dans la moelle épinière, et d’autre part contrôlent l’activité de neurones à ocytocine libérant la molécule dans la circulation sanguine. Notre étude sur la séparation maternelle démontre qu’elle induit une hypersensibilité à la douleur à l’âge adulte et un dysfonctionnement de l’analgésie endogène ocytocinergique

Giere et al_MS submitted to EJN

Graphpad file containing data shown in manuscript</p

Overexpression of chloride importer NKCC1 contributes to the sensory-affective and sociability phenotype of rats following neonatal maternal separation

International audienceBackground: Early life stress is known to affect the development of the nervous system and its function at a later age. It increases the risk to develop psychiatric disorders as well as chronic pain and its associated affective comorbidities across the lifespan. GABAergic inhibition is important for the regulation of central function and related behaviors, including nociception, anxiety or social interactions, and requires low intracellular chloride levels. Of particular interest, the oxytocinergic (OTergic) system exerts potent anxiolytic, analgesic and pro-social properties and is known to be involved in the regulation of chloride homeostasis and to be impaired following early life stress.Methods: We used behavioral measures to evaluate anxiety, social interactions and pain responses in a rat model of neonatal maternal separation (NMS). Using quantitative PCR, we investigated whether NMS was associated with alterations in the expression of chloride transporters in the cerebrum and spinal cord. Finally, we evaluated the contribution of OTergic signaling and neuro-inflammatory processes in the observed phenotype.Results: NMS animals displayed a long-lasting upregulation of chloride importer Na-K-Cl cotransporter type 1 (NKCC1) expression in the cerebrum and spinal cord. Neonatal administration of the NKCC1 inhibitor bumetanide or oxytocin successfully normalized the anxiety-like symptoms and the lack of social preference observed in NMS animals. Phenotypic alterations were associated with a pro-inflammatory state which could contribute to NKCC1 upregulation.Conclusions: This work suggests that an impaired chloride homeostasis, linked to oxytocin signaling dysfunction and to neuro-inflammatory processes, could contribute to the sensori-affective phenotype following NMS

Effect of Virtual Reality Hypnosis on Pain Threshold and Neurophysiological and Autonomic Biomarkers in Healthy Volunteers: Prospective Randomized Crossover Study

Background: Virtual reality hypnosis (VRH) is a promising tool to reduce pain. However, the benefits of VRH on pain perception and on the physiological expression of pain require further investigation.Objective: In this study, we characterized the effects of VRH on the heat pain threshold among adult healthy volunteers while monitoring several physiological and autonomic functions.Methods: Sixty healthy volunteers were prospectively included to receive nociceptive stimulations. The first set of thermal stimuli consisted of 20 stimulations at 60°C (duration 500 milliseconds) to trigger contact heat evoked potentials (CHEPs). The second set of thermal stimuli consisted of ramps (1°C/second) to determine the heat pain threshold of the participants. Electrocardiogram, skin conductance responses, respiration rate, as well as the analgesia nociception index were also recorded throughout the experiment.Results: Data from 58 participants were analyzed. There was a small but significant increase in pain threshold in VRH (50.19°C, SD 1.98°C) compared to that in the control condition (mean 49.45°C, SD 1.87; P0.5; n=22 and n=52, respectively). During VRH, participants exhibited a clear reduction in their autonomic sympathetic tone, as shown by the lower number of nonspecific skin conductance peak responses (P<.001, two-way analysis of variance; n=39) and by an increase in the analgesia nociception index (P<.001, paired t-test; n=40).Conclusions: The results obtained in this study support the idea that VRH administration is effective at increasing heat pain thresholds and impacts autonomic functions among healthy volunteers. As a nonpharmacological intervention, VRH has beneficial action on acute experimental heat pain. This beneficial action will need to be evaluated for the treatment of other types of pain, including chronic pain

Pharmacological rescue of nociceptive hypersensitivity and oxytocin analgesia impairment in a rat model of neonatal maternal separation

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A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing

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