A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch
Ramsden CE, Domenichiello AF, Yuan ZX, Sapio MR, Keyes GS, Mishra SK, Gross JR, Majchrzak-Hong S, Zamora D, Horowitz MS, Davis JM, Sorokin AV, Dey A, LaPaglia DM, Wheeler JJ, Vasko MR, Mehta NN, Mannes AJ, Iadarola MJ
Science signaling · 67 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Case-control study (indexed by PubMed)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institutes of Health
- University or hospital
- Center for Neuroscience and Regenerative Medicine
- Government
- National Institute on Alcohol Abuse and Alcoholism
- Government
- National Institute on Aging
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Institute of Neurological Disorders and Stroke
- Government
- National Center for Research Resources
- Government
- NIH Clinical Center
- Government
- NINDS NIH HHS
- Government
- NCRR NIH HHS
- Government
- Intramural NIH HHS
- Grants
- National Institute of Neurological Disorders and Stroke (R01NS069915); National Institutes of Health (1c06rr015481-01); National Center for Research Resources (C06 RR015481); NIH Clinical Center (award341871); National Institutes of Health (Z99 AG999999); National Center for Research Resources (C06 RR015481-01); National Institute on Alcohol Abuse and Alcoholism (award311572); National Institute on Aging (award311571); National Institutes of Health (NS069915)
Based on 11 listed funder(s).
Publication
- Published
- 2017-08-22 · Sci Signal · vol. 10 · issue 493
- Publisher
- American Association for the Advancement of Science
- Cited
- 78 citations · more than 97% of similar papers · 5.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 56 works
- Access
- Open access (repository copy)
- Research areas
- Fatty Acid Research and Health · Muscle metabolism and nutrition · Adipose Tissue and Metabolism
- Keywords
- Linoleic acid, Chemistry, Neuroscience, Medicine, Pharmacology, Computational biology, Biology, Biochemistry, Fatty acid
- MeSH
- nociceptors, skin, animals, humans, mice, rats, rats, sprague-dawley, pain, pruritus, psoriasis, inflammation, linoleic acid, receptors, calcitonin gene-related peptide, case-control studies, systems analysis, adult, aged, aged, 80 and over, middle aged, female, male, sensory receptor cells, in vitro techniques
19 authors
From US
- Christopher E. Ramsden · correspondingUniversity of North Carolina at Chapel Hill; National Institute on Alcohol Abuse and Alcoholism; National Institute on Aging
- Anthony F. DomenichielloUniformed Services University of the Health Sciences; National Institute on Aging; Center for Neuroscience and Regenerative Medicine
- Zhi‐Xin YuanNational Institute on Aging
- Matthew R. SapioNational Institutes of Health Clinical Center
- Gregory S. KeyesNational Institute on Aging
- Santosh Kumar MishraNorth Carolina State University
Abstract
Chronic pain and itch are common hypersensitivity syndromes that are affected by endogenous mediators. We applied a systems-based, translational approach to predict, discover, and characterize mediators of pain and itch that are regulated by diet and inflammation. Profiling of tissue-specific precursor abundance and biosynthetic gene expression predicted that inflamed skin would be abundant in four previously unknown 11-hydroxy-epoxy- or 11-keto-epoxy-octadecenoate linoleic acid derivatives and four previously identified 9- or 13-hydroxy-epoxy- or 9- or 13-keto-epoxy-octadecenoate linoleic acid derivatives. All of these mediators were confirmed to be abundant in rat and human skin by mass spectrometry. However, only the two 11-hydroxy-epoxy-octadecenoates sensitized rat dorsal root ganglion neurons to release more calcitonin gene-related peptide (CGRP), which is involved in pain transmission, in response to low pH (which mimics an inflammatory state) or capsaicin (which activates ion channels involved in nociception). The two 11-hydroxy-epoxy-octadecenoates share a 3-hydroxy-Z-pentenyl-E-epoxide moiety, thus suggesting that this substructure could mediate nociceptor sensitization. In rats, intradermal hind paw injection of 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate elicited C-fiber-mediated sensitivity to thermal pain. In a randomized trial testing adjunctive strategies to manage refractory chronic headaches, reducing the dietary intake of linoleic acid was associated with decreases in plasma 11-hydroxy-12,13-trans-epoxy-(9Z)-octadecenoate, which correlated with clinical pain reduction. Human psoriatic skin had 30-fold higher 9-keto-12,13-trans-epoxy-(10E)-octadecenoate compared to control skin, and intradermal injection of this compound induced itch-related scratching behavior in mice. Collectively, these findings define a family of endogenous mediators with potential roles in pain and itch.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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