Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons
Endogenous lipid mediators are proposed to contribute to headache and facial pain by activating trigeminal neurons (TN). We recently identified 11-hydroxy-epoxide- and 11-keto-epoxide derivatives of linoleic acid (LA) that are present in human skin and plasma and potentially contribute to nociceptio...
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doaj-c00e0c75625b44efb2d6ecd8d4ba33d22020-11-25T03:18:12ZengElsevierNeurobiology of Pain2452-073X2020-01-017Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neuronsSuzanne Doolen0Gregory S. Keyes1Christopher E. Ramsden2Department of Physiology, University of Kentucky, 800 Rose Street, Lexington, KY 40536-0298, United States; Corresponding author at: Department of Medicine, University of Pittsburgh, 100 Technology Dr., Pittsburgh, PA 15219, USA.Lipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USALipid Peroxidation Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20814, USAEndogenous lipid mediators are proposed to contribute to headache and facial pain by activating trigeminal neurons (TN). We recently identified 11-hydroxy-epoxide- and 11-keto-epoxide derivatives of linoleic acid (LA) that are present in human skin and plasma and potentially contribute to nociception. Here we expand upon initial findings by examining the effects of 11-hydroxy- and 11-keto-epoxide-LA derivatives on TN activation in comparison to LA, the LA derivative [9-hydroxy-octadecadienoic acid (9-HODE)] and prostaglandin E2 (PGE2). 11-hydroxy- and 11-keto-epoxide-LA derivatives elicited Ca2+ transients in TN subpopulations. The proportion of neurons responding to test compounds (5 μM, 5 min) ranged from 16.2 ± 3.8 cells (11 K-9,10E-LA) to 34.1 ± 2.4 cells (11H-12,13E-LA). LA and 9-HODE (5 μM, 5 min) elicited responses in 11.6 ± 3.1% and 9.7 ± 3.4% of neurons, respectively. 11H-12,13E-LA, 11K-12,13E-LA, and 11H-9,10E-LA produced Ca2+ responses in significantly higher proportions of neurons compared to either LA or 9-HODE (F (6, 36) = 5.12, P = 0.0007). 11H-12,13E-LA and 11H-9,10E-LA increased proportions of responsive neurons in a concentration-dependent fashion, similar to PGE2. Most sensitive neurons responded to additional algesic agents (32.9% to capsaicin, 40.1% to PGE2, 58.0% to AITC), however 20.6% did not respond to any other agent. In summary, 11-hydroxy-epoxide derivatives of LA increase trigeminal neuron excitability, suggesting a potential role in headache or facial pain.http://www.sciencedirect.com/science/article/pii/S2452073X20300040PainHyperalgesiaLinoleic acidPeroxidationOxylipin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Suzanne Doolen Gregory S. Keyes Christopher E. Ramsden |
spellingShingle |
Suzanne Doolen Gregory S. Keyes Christopher E. Ramsden Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons Neurobiology of Pain Pain Hyperalgesia Linoleic acid Peroxidation Oxylipin |
author_facet |
Suzanne Doolen Gregory S. Keyes Christopher E. Ramsden |
author_sort |
Suzanne Doolen |
title |
Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
title_short |
Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
title_full |
Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
title_fullStr |
Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
title_full_unstemmed |
Hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
title_sort |
hydroxy-epoxide and keto-epoxide derivatives of linoleic acid activate trigeminal neurons |
publisher |
Elsevier |
series |
Neurobiology of Pain |
issn |
2452-073X |
publishDate |
2020-01-01 |
description |
Endogenous lipid mediators are proposed to contribute to headache and facial pain by activating trigeminal neurons (TN). We recently identified 11-hydroxy-epoxide- and 11-keto-epoxide derivatives of linoleic acid (LA) that are present in human skin and plasma and potentially contribute to nociception. Here we expand upon initial findings by examining the effects of 11-hydroxy- and 11-keto-epoxide-LA derivatives on TN activation in comparison to LA, the LA derivative [9-hydroxy-octadecadienoic acid (9-HODE)] and prostaglandin E2 (PGE2). 11-hydroxy- and 11-keto-epoxide-LA derivatives elicited Ca2+ transients in TN subpopulations. The proportion of neurons responding to test compounds (5 μM, 5 min) ranged from 16.2 ± 3.8 cells (11 K-9,10E-LA) to 34.1 ± 2.4 cells (11H-12,13E-LA). LA and 9-HODE (5 μM, 5 min) elicited responses in 11.6 ± 3.1% and 9.7 ± 3.4% of neurons, respectively. 11H-12,13E-LA, 11K-12,13E-LA, and 11H-9,10E-LA produced Ca2+ responses in significantly higher proportions of neurons compared to either LA or 9-HODE (F (6, 36) = 5.12, P = 0.0007). 11H-12,13E-LA and 11H-9,10E-LA increased proportions of responsive neurons in a concentration-dependent fashion, similar to PGE2. Most sensitive neurons responded to additional algesic agents (32.9% to capsaicin, 40.1% to PGE2, 58.0% to AITC), however 20.6% did not respond to any other agent. In summary, 11-hydroxy-epoxide derivatives of LA increase trigeminal neuron excitability, suggesting a potential role in headache or facial pain. |
topic |
Pain Hyperalgesia Linoleic acid Peroxidation Oxylipin |
url |
http://www.sciencedirect.com/science/article/pii/S2452073X20300040 |
work_keys_str_mv |
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