Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch

• Published in: Nature communications Vol. 7; no. 1; p. 13092
• Main Authors: Morales-Lázaro, Sara L., Llorente, Itzel, Sierra-Ramírez, Félix, López-Romero, Ana E., Ortíz-Rentería, Miguel, Serrano-Flores, Barbara, Simon, Sidney A., Islas, León D., Rosenbaum, Tamara
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-10-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 631/378/2620/410; 631/45/269/1153; 64/60; 82/1; 9/74; Amino Acid Sequence; Animals; Binding Sites; Capsaicin - pharmacology; Fatty acids; HEK293 Cells; Histamine; Humanities and Social Sciences; Humans; Ion Channel Gating - drug effects; Mice, Inbred C57BL; Molecular Docking Simulation; multidisciplinary; Neurosciences; Oleic Acid - pharmacology; Oleic Acid - therapeutic use; Pain; Pain - drug therapy; Pain - pathology; Physiology; Pruritus - drug therapy; Pruritus - pathology; Rats; Science; Science (multidisciplinary); TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - chemistry; TRPV Cation Channels - metabolism; Mexico
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13092

The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation.
TRPV1 channels are known to mediate pathological pain and itch. Here, the authors find a naturally occurring fatty acid, oleic acid, acts as a TRPV1 antagonist and can modulate capsaicin and histamine-mediated pain and itch response in mouse models.