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Cell Rep. 2017 Nov 7;21(6):1681-1691. doi: 10.1016/j.celrep.2017.10.063.

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1.

Author information

1
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, 1 Illini Drive, Peoria, IL 61605, USA.
2
Instituto de Fisiologia, Facultad de Medicina, Universidad Austral de Chile, and Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Valdivia 5110566, Chile.
3
Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK.
4
Department of Anesthesia, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, Brazil.
5
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, 1 Illini Drive, Peoria, IL 61605, USA; College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215123, China.
6
Ion Channel Research Unit, Duke University Medical Center, Durham, NC 27710, USA.
7
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, 5850 College Street, P.O. Box 15000, Halifax, NS B3H 4R2, Canada.
8
Department of Anesthesia, Friedrich-Alexander University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
9
Department of Chemistry, King's College London, Britannia House, 7 Trinity Street, London, SE1 1DB, UK; Chemistry Research Laboratory, Mansfield Road, University of Oxford, Oxford, OX1 3TA, UK.
10
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, 1 Illini Drive, Peoria, IL 61605, USA. Electronic address: zakharel@uic.edu.

Abstract

Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

KEYWORDS:

MD simulations; TRPV1 ion channel; molecular dynamics simulations; nociception; oxytocin; oxytocin receptor; planar lipid bilayers; transient receptor potential vanilloid 1

PMID:
29117570
PMCID:
PMC5701661
DOI:
10.1016/j.celrep.2017.10.063
[Indexed for MEDLINE]
Free PMC Article

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