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

Marina Eliava; Meggane Melchior; H Sophie Knobloch-Bollmann; Jérôme Wahis; Miriam da Silva Gouveia; Yan Tang; Alexandru Cristian Ciobanu; Rodrigo Triana Del Rio; Lena C Roth; Ferdinand Althammer; Virginie Chavant; Yannick Goumon; Tim Gruber; Nathalie Petit-Demoulière; Marta Busnelli; Bice Chini; Linette L Tan; Mariela Mitre; Robert C Froemke; Moses V Chao; Günter Giese; Rolf Sprengel; Rohini Kuner; Pierrick Poisbeau; Peter H Seeburg; Ron Stoop; Alexandre Charlet; Valery Grinevich

doi:10.1016/j.neuron.2016.01.041

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

Neuron. 2016 Mar 16;89(6):1291-1304. doi: 10.1016/j.neuron.2016.01.041. Epub 2016 Mar 3.

Authors

Marina Eliava¹, Meggane Melchior², H Sophie Knobloch-Bollmann³, Jérôme Wahis², Miriam da Silva Gouveia¹, Yan Tang⁴, Alexandru Cristian Ciobanu⁵, Rodrigo Triana Del Rio⁵, Lena C Roth³, Ferdinand Althammer¹, Virginie Chavant², Yannick Goumon², Tim Gruber³, Nathalie Petit-Demoulière², Marta Busnelli⁶, Bice Chini⁷, Linette L Tan⁸, Mariela Mitre⁹, Robert C Froemke⁹, Moses V Chao⁹, Günter Giese¹⁰, Rolf Sprengel¹⁰, Rohini Kuner⁸, Pierrick Poisbeau², Peter H Seeburg¹⁰, Ron Stoop⁵, Alexandre Charlet¹¹, Valery Grinevich¹²

Affiliations

¹ 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.
² Institut of Cellular and Integrative Neurosciences (INCI) UPR3212, Centre National de la Recherche Scientifique (CNRS), University of Strasbourg, Strasbourg 67084, France.
³ 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.
⁴ 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.
⁵ Center for Psychiatric Neurosciences, Hôpital de Cery, Lausanne University Hospital (CHUV), Lausanne 1008, Switzerland.
⁶ National Research Council, Institute of Neuroscience, Milan 20129, Italy.
⁷ National Research Council, Institute of Neuroscience, Milan 20129, Italy; Humanitas Clinical and Research Center, Rozzano 20089, Italy.
⁸ Department for Molecular Pharmacology and Molecular Medicine Partnership Unit with European Molecular Biology Laboratories, Institute of Pharmacology, Heidelberg University, Heidelberg 69120, Germany.
⁹ Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
¹⁰ Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
¹¹ 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.
¹² 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Animals
Cholecystokinin / pharmacology
Disease Models, Animal
Excitatory Amino Acid Antagonists / pharmacology
Gene Expression Regulation / genetics
Gene Expression Regulation / physiology
Inflammation / chemically induced
Inflammation / complications
Neural Pathways / drug effects
Neural Pathways / physiology
Neuralgia / blood*
Neuralgia / drug therapy
Neuralgia / pathology
Neuralgia / physiopathology*
Neurons / physiology*
Oxytocin / blood
Oxytocin / genetics
Oxytocin / metabolism*
Paraventricular Hypothalamic Nucleus / cytology*
Quinoxalines / pharmacology
Rats
Rats, Wistar
Receptors, Oxytocin / genetics
Receptors, Oxytocin / metabolism
Spinal Cord / cytology
Supraoptic Nucleus / cytology*
Transduction, Genetic
Vasopressins / genetics
Vasopressins / metabolism
Vesicular Glutamate Transport Protein 2 / metabolism

Substances

Excitatory Amino Acid Antagonists
Quinoxalines
Receptors, Oxytocin
Slc17a6 protein, rat
Vesicular Glutamate Transport Protein 2
Vasopressins
2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
Oxytocin
Cholecystokinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding