4.4 Article

Molecular Pathways Linking Oxylipins to Nociception in Rats

期刊

JOURNAL OF PAIN
卷 22, 期 3, 页码 275-299

出版社

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.jpain.2020.09.001

关键词

Oxylipin; liquid chromatography tandem-mass spectrometry; lipids; pain; RNASeq

资金

  1. National Institute on Aging
  2. National Institute on Alcohol Abuse and Alcoholism
  3. National Center for Complementary and Integrative Health
  4. National Institutes of Health Clinical Center
  5. NIH Benth-to-Bedside Program from NCCIH
  6. Office of Behavioral and Social Sciences

向作者/读者索取更多资源

Oxylipins, lipid peroxidation products, play a role in nociceptive, inflammatory, and vascular responses. Their effects depend on tissue-specific accumulation of polyunsaturated fatty acid precursors and enzyme expression. Technical challenges in studying oxylipins in nociception have led to gaps in knowledge, requiring further research.
Oxylipins are lipid peroxidation products that participate in nociceptive, inflammatory, and vascular responses to injury. Effects of oxylipins depend on tissue-specific differences in accumulation of precursor polyunsaturated fatty acids and the expression of specific enzymes to transform the precursors. The study of oxylipins in nociception has presented technical challenges leading to critical knowledge gaps in the way these molecules operate in nociception. We applied a systems-based approach to characterize oxylipin precursor fatty acids, and expression of genes coding for proteins involved in biosynthesis, transport, signaling and inactivation of pro- and antinociceptive oxylipins in pain circuit tissues. We further linked these pathways to nociception by demonstrating intraplantar carrageenan injection induced gene expression changes in oxylipin biosynthetic pathways. We determined functional-biochemical relevance of the proposed pathways in rat hind paw and dorsal spinal cord by measuring basal and stimulated levels of oxylipins throughout the time-course of carrageenan-induced inflammation. Finally, when oxylipins were administered by intradermal injection we observed modulation of nociceptive thermal hypersensitivity, providing a functional-behavioral link between oxylipins, their molecular biosynthetic pathways, and involvement in pain and nociception. Together, these findings advance our understanding of molecular lipidomic systems linking oxylipins and their precursors to nociceptive and inflammatory signaling pathways in rats. Perspective: We applied a systems approach to characterize molecular pathways linking precursor lipids and oxylipins to nociceptive signaling. This systematic, quantitative evaluation of the molecular pathways linking oxylipins to nociception provides a framework for future basic and clinical research investigating the role of oxylipins in pain. (C) Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.

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