Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Yelena Nersesyan; Lusine Demirkhanyan; Deny Cabezas-Bratesco; Victoria Oakes; Ricardo Kusuda; Tyler Dawson; Xiaohui Sun; Chike Cao; Alejandro Martin Cohen; Bharath Chelluboina; Krishna Kumar Veeravalli; Katharina Zimmermann; Carmen Domene; Sebastian Brauchi; Eleonora Zakharian

doi:10.1016/j.celrep.2017.10.063

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Yelena Nersesyan, Lusine Demirkhanyan, Deny Cabezas-Bratesco, Victoria Oakes, Ricardo Kusuda, Tyler Dawson, Xiaohui Sun, Chike Cao, Alejandro Martin Cohen, Bharath Chelluboina, Krishna Kumar Veeravalli, Katharina Zimmermann, Carmen Domene, Sebastian Brauchi, Eleonora Zakharian

Medicine

Research output: Contribution to journal › Article › peer-review

101 Citations (Scopus)

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. Oxytocin is known to suppress painful stimuli of inflammatory origin. Nersesyan et al. now find that oxytocin attenuates pain via the pain-sensing receptor TRPV1.

Original language	English
Pages (from-to)	1681-1691
Number of pages	11
Journal	Cell Reports
Volume	21
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2017.10.063
Publication status	Published - Nov 7 2017

Bibliographical note

Funding Information:
This work was initially supported by the NIH through grant R01GM098052 to E.Z. C.D. and V.O. acknowledge the PRACE initiative for awarding the access to computational resources in ARCHER—the UK National Supercomputing Service ( http://www.archer.ac.uk ), the PDC Centre for High Performance Computing ( PDC-HPC ), CINECA , and the Jülich Supercomputing Center . V.O. was supported by BB/L015269/1 from the Biotechnology and Biological Sciences Research Council and Pfizer Neusentis . S.B. was supported by Anillo Científico ACT-1401 . S.B. is a part of CISNe-UACh and UACh Program for Cell Biology.

Publisher Copyright:
© 2017 The Authors

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

PubMed: MeSH publication types

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10.1016/j.celrep.2017.10.063

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title = "Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1",

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. Oxytocin is known to suppress painful stimuli of inflammatory origin. Nersesyan et al. now find that oxytocin attenuates pain via the pain-sensing receptor TRPV1.",

author = "Yelena Nersesyan and Lusine Demirkhanyan and Deny Cabezas-Bratesco and Victoria Oakes and Ricardo Kusuda and Tyler Dawson and Xiaohui Sun and Chike Cao and Cohen, {Alejandro Martin} and Bharath Chelluboina and Veeravalli, {Krishna Kumar} and Katharina Zimmermann and Carmen Domene and Sebastian Brauchi and Eleonora Zakharian",

note = "Funding Information: This work was initially supported by the NIH through grant R01GM098052 to E.Z. C.D. and V.O. acknowledge the PRACE initiative for awarding the access to computational resources in ARCHER—the UK National Supercomputing Service ( http://www.archer.ac.uk ), the PDC Centre for High Performance Computing ( PDC-HPC ), CINECA , and the J{\"u}lich Supercomputing Center . V.O. was supported by BB/L015269/1 from the Biotechnology and Biological Sciences Research Council and Pfizer Neusentis . S.B. was supported by Anillo Cient{\'i}fico ACT-1401 . S.B. is a part of CISNe-UACh and UACh Program for Cell Biology. Publisher Copyright: {\textcopyright} 2017 The Authors",

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AU - Oakes, Victoria

AU - Kusuda, Ricardo

AU - Dawson, Tyler

AU - Sun, Xiaohui

AU - Cao, Chike

AU - Cohen, Alejandro Martin

AU - Chelluboina, Bharath

AU - Veeravalli, Krishna Kumar

AU - Zimmermann, Katharina

AU - Domene, Carmen

AU - Brauchi, Sebastian

AU - Zakharian, Eleonora

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Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Abstract

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