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

Author

Listed:
  • Mai Iwasaki

    (Institute of Cellular and Integrative Neuroscience)

  • Arthur Lefevre

    (Institute of Cellular and Integrative Neuroscience
    University of Heidelberg
    University of California, San Diego)

  • Ferdinand Althammer

    (University of Heidelberg
    Georgia State University
    University Hospital Heidelberg)

  • Etienne Clauss Creusot

    (Institute of Cellular and Integrative Neuroscience)

  • Olga Łąpieś

    (Institute of Cellular and Integrative Neuroscience)

  • Hugues Petitjean

    (Institute of Cellular and Integrative Neuroscience)

  • Louis Hilfiger

    (Institute of Cellular and Integrative Neuroscience)

  • Damien Kerspern

    (Institute of Cellular and Integrative Neuroscience)

  • Meggane Melchior

    (Institute of Cellular and Integrative Neuroscience)

  • Stephanie Küppers

    (University of Heidelberg)

  • Quirin Krabichler

    (University of Heidelberg)

  • Ryan Patwell

    (University of Heidelberg)

  • Alan Kania

    (University of Heidelberg)

  • Tim Gruber

    (Van Andel Institute)

  • Matthew K. Kirchner

    (Georgia State University)

  • Moritz Wimmer

    (University Hospital Heidelberg)

  • Henning Fröhlich

    (University Hospital Heidelberg)

  • Laura Dötsch

    (University Hospital Heidelberg)

  • Jonas Schimmer

    (University of Heidelberg)

  • Sabine C. Herpertz

    (University of Heidelberg)

  • Beate Ditzen

    (Heidelberg University Hospital
    Ruprecht-Karls University Heidelberg)

  • Christian P. Schaaf

    (University Hospital Heidelberg
    Ruprecht-Karls University Heidelberg)

  • Kai Schönig

    (University of Heidelberg)

  • Dusan Bartsch

    (University of Heidelberg)

  • Anna Gugula

    (Jagiellonian University)

  • Aleksandra Trenk

    (Jagiellonian University)

  • Anna Blasiak

    (Jagiellonian University)

  • Javier E. Stern

    (Georgia State University)

  • Pascal Darbon

    (Institute of Cellular and Integrative Neuroscience)

  • Valery Grinevich

    (University of Heidelberg
    Georgia State University)

  • Alexandre Charlet

    (Institute of Cellular and Integrative Neuroscience)

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.

Suggested Citation

  • Mai Iwasaki & Arthur Lefevre & Ferdinand Althammer & Etienne Clauss Creusot & Olga Łąpieś & Hugues Petitjean & Louis Hilfiger & Damien Kerspern & Meggane Melchior & Stephanie Küppers & Quirin Krabichl, 2023. "An analgesic pathway from parvocellular oxytocin neurons to the periaqueductal gray in rats," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36641-7
    DOI: 10.1038/s41467-023-36641-7
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