Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

• Published in: Cell reports (Cambridge) Vol. 21; no. 6; pp. 1681 - 1691
• Main Authors: Nersesyan, Yelena, Demirkhanyan, Lusine, Cabezas-Bratesco, Deny, Oakes, Victoria, Kusuda, Ricardo, Dawson, Tyler, Sun, Xiaohui, Cao, Chike, Cohen, Alejandro Martin, Chelluboina, Bharath, Veeravalli, Krishna Kumar, Zimmermann, Katharina, Domene, Carmen, Brauchi, Sebastian, Zakharian, Eleonora
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.11.2017; Elsevier
• Subjects: MD simulations; molecular dynamics simulations; nociception; oxytocin; oxytocin receptor; planar lipid bilayers; transient receptor potential vanilloid 1; TRPV1 ion channel; molecular dynamics simulations; oxytocin; transient receptor potential vanilloid 1; TRPV1 ion channel; oxytocin receptor; MD simulations; nociception; planar lipid bilayers
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.10.063

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. [Display omitted] •TRPV1 acts as an ionotropic oxytocin receptor in cells•Oxytocin potentiates TRPV1 in cells and lipid bilayers•Oxytocin interacts with TRPV1 at the extracellular pore loop region•Oxytocin attenuates capsaicin-induced nociception via TRPV1 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.