A new population of parvocellular oxytocin neurons controlling magnocellular neuron activity and inflammatory pain processing
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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.
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In rodents, neurons in the PVN are the main source of OXT projections to the brain.
“In rodents, neurons in the PVN are the main source of OXT projections to the brain [22,69].”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [69]
Previously parvocellular OT neurons had only been directly implicated in non-social functions.
“previously parvocellular OT neurons had only been directly implicated in non-social functions (e.g. feeding, yawning, erection, cardiovascular function, pain (Althammer and Grinevich, 2017; Eliava et al., 2016; Melis et al., 1986; Petersson, 2002; Valassi et al., 2008))”
From Parallel social information processing circuits are differentially impacted in autism (2020) · cites this paper as Eliava et al., 2016
Atosiban mimics the inhibitory effect of OT on sensory neurons of the spinal cord, providing evidence of its unique agonist activity on restricted OTR signaling pathways.
“Atosiban mimicked the inhibitory effect of OT on sensory neurons of the spinal cord, providing clear evidence of its unique agonist activity on restricted OTR signaling pathways (57).”
From Oxytocin receptors in the anteromedial bed nucleus of the stria terminalis promote stress-induced social avoidance in female California mice (2018) · cites this paper as [57]
Atosiban activates Gi-mediated pathways in vitro and in vivo.
“Interestingly, the OTR ligand atosiban, considered to be an OTR antagonist, actually activates Gi-mediated pathways in vitro (36, 38) and in vivo (57).”
From Oxytocin receptors in the anteromedial bed nucleus of the stria terminalis promote stress-induced social avoidance in female California mice (2018) · cites this paper as [57]
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The psychophysiology of music-based interventions and the experience of pain
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Targeting the Oxytocin System: New Pharmacotherapeutic Approaches
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Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis
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Self-citationThe Lateral Hypothalamus: An Uncharted Territory for Processing Peripheral Neurogenic Inflammation
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Neural functions of hypothalamic oxytocin and its regulation
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Self-citationNeuropeptide Regulation of Social Attachment: The Prairie Vole Model
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The oxytocin signaling complex reveals a molecular switch for cation dependence
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- Authors
- Eliava, M., Melchior, M., Knobloch-Bollmann, H. S., Wahis, J., da Silva Gouveia, M., Tang, Y., Ciobanu, A. C., Triana del Rio, R., Roth, L. C., Althammer, F., Chavant, V., Goumon, Y., Gruber, T., Petit-Demoulière, N., Busnelli, M., Chini, B., Tan, L. L., Mitre, M., Froemke, R. C., Chao, M. V., Giese, G., Sprengel, R., Kuner, R., Poisbeau, P., Seeburg, P. H., Stoop, R., Charlet, A., & Grinevich, V.
- Affiliations
- German Cancer Research Center (DE)
- Centre National de la Recherche Scientifique (FR)
- Centre Hospitalier Universitaire Vaudois (CH)
- National Research Council (IT)
- Heidelberg University (DE)
- NYU Langone Health (US)
- Max Planck Institute for Medical Research (DE)
- Corresponding author
- Charlet, Alexandre
- Grinevich, Valery
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 89
- Issue
- 6
- Pages
- 1291-1304
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5679079
- OpenAlex
- W2292055541
- Cited by
- 409
- References
- 59
- Citations by year
- 2026: 26 · 2025: 35 · 2024: 28 · 2023: 40 · 2022: 50 · 2021: 63 · 2020: 38 · 2019: 36 · 2018: 42 · 2017: 36 · 2016: 14
- FWCI
- 34.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Max Planck Digital Library (submittedVersion)
- IRIS (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- European Commission (334455)
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft (GR 3619/4‐1)
- Agence Nationale de la Recherche (ANR-10-IDEX-0002)
- Université de Strasbourg
- Campus France
- National Institute on Deafness and Other Communication Disorders (R01DC012557)
- National Institute of General Medical Sciences (T32GM007308)
- National Institute of Neurological Disorders and Stroke (T32NS086750)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, paraventricular nucleus, supraoptic nucleus, spinal cord nociception, inflammatory pain, analgesia, collateral projections, hypothalamus, oxytocin release
- MeSH terms
- Action Potentials, Animals, Cholecystokinin, Disease Models, Animal, Gene Expression Regulation, Inflammation, Neural Pathways, Neuralgia, Neurons, Oxytocin, Paraventricular Hypothalamic Nucleus, Quinoxalines, Spinal Cord, Supraoptic Nucleus, Transduction, Genetic, Vasopressins, Rats, Wistar, Receptors, Oxytocin, Excitatory Amino Acid Antagonists, Vesicular Glutamate Transport Protein 2, Rats
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