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 Nunez, Sebastian Brauchi, Eleonora Zakharian

Research output: Contribution to journalArticlepeer-review

39 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.

Original languageEnglish
Pages (from-to)1681-1691
Number of pages11
JournalCell Reports
Volume21
Issue number6
Early online date7 Nov 2017
DOIs
Publication statusE-pub ahead of print - 7 Nov 2017

Keywords

  • Journal Article

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