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 citas
Etiquetas de revisión
Sin ajuste declarado por estilo de vidaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio de casos y controles (indexado por PubMed)
- Estudiado en
- Animales
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Universidad u hospital
- Center for Neuroscience and Regenerative Medicine
- Gobierno
- National Institute on Alcohol Abuse and Alcoholism
- Gobierno
- National Institute on Aging
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- National Center for Research Resources
- Gobierno
- NIH Clinical Center
- Gobierno
- NINDS NIH HHS
- Gobierno
- NCRR NIH HHS
- Gobierno
- Intramural NIH HHS
- Subvenciones
- 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)
Según 11 financiadores declarados.
Publicación
- Publicado
- 2017-08-22 · Sci Signal · vol. 10 · número 493
- Editorial
- American Association for the Advancement of Science
- Citado
- 78 citas · más que el 97% de estudios similares · 5.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 56 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Fatty Acid Research and Health · Muscle metabolism and nutrition · Adipose Tissue and Metabolism
- Palabras clave
- 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 autores
- Christopher E. Ramsden🇺🇸 · autor de correspondenciaUniversity of North Carolina at Chapel Hill; National Institute on Alcohol Abuse and Alcoholism; National Institute on Aging
- Anthony F. Domenichiello🇺🇸Uniformed Services University of the Health Sciences; National Institute on Aging; Center for Neuroscience and Regenerative Medicine
- Zhi‐Xin Yuan🇺🇸National Institute on Aging
- Matthew R. Sapio🇺🇸National Institutes of Health Clinical Center
- Gregory S. Keyes🇺🇸National Institute on Aging
- Santosh Kumar Mishra🇺🇸North Carolina State University
- Jacklyn R. Gross🇺🇸National Institutes of Health Clinical Center
- Sharon F. Majchrzak‐Hong🇺🇸National Institute on Alcohol Abuse and Alcoholism
- Daisy Zamora🇺🇸University of North Carolina at Chapel Hill; National Institute on Aging
- Mark S. Horowitz🇺🇸National Institute on Aging
- John M. Davis🇺🇸University of Illinois Chicago; National Institute on Aging
- Alexander V. Sorokin🇺🇸National Heart, Lung, and Blood Institute
- Amit Dey🇺🇸National Heart, Lung, and Blood Institute
- Danielle M. LaPaglia🇺🇸National Institutes of Health Clinical Center
- Joshua J. Wheeler🇺🇸North Carolina State University
- Michael R. Vasko🇺🇸Indiana University School of Medicine; Indiana University – Purdue University Indianapolis
- Nehal N. Mehta🇺🇸National Heart, Lung, and Blood Institute
- Andrew J. Mannes🇺🇸National Institutes of Health Clinical Center
- Michael J. Iadarola🇺🇸National Institutes of Health Clinical Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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