2. Academic Validation
  3. An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats

An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats

  • Nat Commun. 2023 Feb 24;14(1):1066. doi: 10.1038/s41467-023-36641-7.
Mai Iwasaki # 1,  Arthur Lefevre # 1 2 3,  Ferdinand Althammer # 2 4 5,  Etienne Clauss Creusot # 1,  Olga Łąpieś 1,  Hugues Petitjean 1,  Louis Hilfiger 1,  Damien Kerspern 1,  Meggane Melchior 1,  Stephanie Küppers 2,  Quirin Krabichler 2,  Ryan Patwell 2,  Alan Kania 2,  Tim Gruber 6,  Matthew K Kirchner 4,  Moritz Wimmer 5,  Henning Fröhlich 5,  Laura Dötsch 5,  Jonas Schimmer 2,  Sabine C Herpertz 7,  Beate Ditzen 8 9,  Christian P Schaaf 5 9,  Kai Schönig 10,  Dusan Bartsch 10,  Anna Gugula 11,  Aleksandra Trenk 11,  Anna Blasiak 11,  Javier E Stern 4,  Pascal Darbon 1,  Valery Grinevich 12 13,  Alexandre Charlet 14
Affiliations

Affiliations

  • 1 Centre National de la Recherche Scientifique and University of Strasbourg, Institute of Cellular and Integrative Neuroscience, 67000, Strasbourg, France.
  • 2 Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, 68159, Germany.
  • 3 Cortical Systems and Behavior Laboratory, University of California, San Diego, La Jolla, CA, 92093, USA.
  • 4 Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA.
  • 5 Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
  • 6 Van Andel Institute, Grand Rapids, MI, USA.
  • 7 Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, 69115, Heidelberg, Germany.
  • 8 Institute of Medical Psychology, Heidelberg University Hospital, 69115, Heidelberg, Germany.
  • 9 Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
  • 10 Department of Molecular Biology, Central Institute of Mental Health, University of Heidelberg, Mannheim, 68159, Germany.
  • 11 Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, 30-387, Poland.
  • 12 Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, 68159, Germany. valery.grinevich@zi-mannheim.de.
  • 13 Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, USA. valery.grinevich@zi-mannheim.de.
  • 14 Centre National de la Recherche Scientifique and University of Strasbourg, Institute of Cellular and Integrative Neuroscience, 67000, Strasbourg, France. acharlet@unistra.fr.
  • # Contributed equally.
PMID: 36828816 DOI: 10.1038/s41467-023-36641-7
Abstract

The hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic effects via central and peripheral action. However, the precise analgesic pathways recruited by OT are largely elusive. Here we discovered a subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells targeted by OT projections are GABAergic. Ex vivo stimulation of parvocellular OT axons in the vlPAG induced local OT release, as measured with OT sensor GRAB. In vivo, optogenetically-evoked axonal OT release in the vlPAG of as well as chemogenetic activation of OTR vlPAG neurons resulted in a long-lasting increase of vlPAG neuronal activity. This lead to an indirect suppression of sensory neuron activity in the spinal cord and strong analgesia in both female and male rats. Altogether, we describe an OT-vlPAG-spinal cord circuit that is critical for analgesia in both inflammatory and neuropathic pain models.

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