title: A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.
abstract: Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Eliava
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Meggane
authors.initials: M
authors.lastname: Melchior
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany; Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: H Sophie
authors.initials: HS
authors.lastname: Knobloch-Bollmann
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Wahis
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: da Silva Gouveia
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany; Institute of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Center for Psychiatric Neurosciences, Hôpital de Cery, Lausanne University Hospital (CHUV), Lausanne 1008, Switzerland.
authors.forename: Alexandru Cristian
authors.initials: AC
authors.lastname: Ciobanu
authors.affiliation: Center for Psychiatric Neurosciences, Hôpital de Cery, Lausanne University Hospital (CHUV), Lausanne 1008, Switzerland.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Triana Del Rio
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany; Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: Lena C
authors.initials: LC
authors.lastname: Roth
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Althammer
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Chavant
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Goumon
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany; Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Gruber
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Petit-Demoulière
authors.affiliation: National Research Council, Institute of Neuroscience, Milan 20129, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Busnelli
authors.affiliation: National Research Council, Institute of Neuroscience, Milan 20129, Italy; Humanitas Clinical and Research Center, Rozzano 20089, Italy.
authors.forename: Bice
authors.initials: B
authors.lastname: Chini
authors.affiliation: Department for Molecular Pharmacology and Molecular Medicine Partnership Unit with European Molecular Biology Laboratories, Institute of Pharmacology, Heidelberg University, Heidelberg 69120, Germany.
authors.forename: Linette L
authors.initials: LL
authors.lastname: Tan
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Mariela
authors.initials: M
authors.lastname: Mitre
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Froemke
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
authors.affiliation: Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Giese
authors.affiliation: Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.affiliation: Department for Molecular Pharmacology and Molecular Medicine Partnership Unit with European Molecular Biology Laboratories, Institute of Pharmacology, Heidelberg University, Heidelberg 69120, Germany.
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
authors.forename: Pierrick
authors.initials: P
authors.lastname: Poisbeau
authors.affiliation: Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.affiliation: Center for Psychiatric Neurosciences, Hôpital de Cery, Lausanne University Hospital (CHUV), Lausanne 1008, Switzerland.
authors.forename: Ron
authors.initials: R
authors.lastname: Stoop
authors.affiliation: Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France; University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg 67000, France. Electronic address: acharlet@unistra.fr.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Charlet
authors.affiliation: Schaller Research Group on Neuropeptides at German Cancer Research Center (DKFZ) and Cell Network Cluster of Excellence at the University of Heidelberg, Heidelberg 69120, Germany; Max Planck Institute for Medical Research, Heidelberg 69120, Germany; Central Institute of Mental Health (ZI), Mannheim 68159, Germany. Electronic address: v.grinevich@dkfz-heidelberg.de.
authors.forename: Valery
authors.initials: V
authors.lastname: Grinevich
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013495:Supraoptic Nucleus / Q000166:cytology*; D014161:Transduction, Genetic; D014667:Vasopressins / Q000235:genetics / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018045:Receptors, Oxytocin; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D014667:Vasopressins; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D010121:Oxytocin; D002766:Cholecystokinin