Endogenous Derivatives of Linoleic Acid and their Stable Analogs Are Potential Pain Mediators.

Autor:	Wheeler JJ; Department of Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, North Carolina, USA.; Comparative Medicine Institute, NC State University, Raleigh, North Carolina, USA., Domenichiello AF; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, Maryland, USA., Jensen JR; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, Maryland, USA.; Neurosciences Graduate Program, University of California San Diego, La Jolla, California, USA., Keyes GS; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, Maryland, USA., Maiden KM; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, Maryland, USA.; Obstetrics-Gynecology Program, School of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA., Davis JM; Department of Psychiatry, Psychiatry College of Medicine, University of Illinois at Chicago, Chicago, Ilinois, USA., Ramsden CE; Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore, Maryland, USA., Mishra SK; Department of Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, North Carolina, USA.; Comparative Medicine Institute, NC State University, Raleigh, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	JID innovations : skin science from molecules to population health [JID Innov] 2022 Dec 26; Vol. 3 (2), pp. 100177. Date of Electronic Publication: 2022 Dec 26 (Print Publication: 2023).
DOI:	10.1016/j.xjidi.2022.100177
Abstrakt:	Psoriasis is characterized by intense pruritus, with a subset of individuals with psoriasis experiencing thermal hypersensitivity. However, the pathophysiology of thermal hypersensitivity in psoriasis and other skin conditions remains enigmatic. Linoleic acid is an omega-6 fatty acid that is concentrated in the skin, and oxidation of linoleic acid into metabolites with multiple hydroxyl and epoxide functional groups has been shown to play a role in skin barrier function. Previously, we identified several linoleic acid‒derived mediators that were more concentrated in psoriatic lesions, but the role of these lipids in psoriasis remains unknown. In this study, we report that two such compounds-9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate-are present as free fatty acids and induce nociceptive behavior in mice but not in rats. By chemically stabilizing 9,10-epoxy-13-hydroxy-octadecenoate and 9,10,13-trihydroxy-octadecenoate through the addition of methyl groups, we observed pain and hypersensitization in mice. The nociceptive responses suggest an involvement of the TRPA1 channel, whereas hypersensitive responses induced by these mediators may require both TRPA1 and TRPV1 channels. Furthermore, we showed that 9,10,13-trihydroxy-octadecenoate‒induced calcium transients in sensory neurons are mediated through the Gβγ subunit of an unidentified G-protein coupled receptor (GPCR). Overall, mechanistic insights from this study will guide the development of potential therapeutic targets for the treatment of pain and hypersensitivity. (© 2022 The Authors.)
Databáze:	MEDLINE
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