期刊
JOURNAL OF NEUROSCIENCE
卷 34, 期 46, 页码 15184-15191出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3475-14.2014
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资金
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute of Environmental Health Sciences
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Neurological Disorders and Stroke
Cells in injured and inflamed tissues produce a number of proalgesic lipid-derived mediators, which excite nociceptive neurons by activating selective G-protein-coupled receptors or ligand-gated ion channels. Recent work has shown that these proalgesic factors are counteracted by a distinct group of lipid molecules that lower nociceptor excitability and attenuate nociception in peripheral tissues. Analgesic lipid mediators include endogenous agonists of cannabinoid receptors (endocannabinoids), lipid-amide agonists of peroxisome proliferator-activated receptor-alpha, and products of oxidative metabolism of polyunsaturated fatty acids via cytochrome P-450 and other enzyme pathways. Evidence indicates that these lipid messengers are produced and act at different stages of inflammation and the response to tissue injury, and may be part of a peripheral gating mechanism that regulates the access of nociceptive information to the spinal cord and the brain. Growing knowledge about this peripheral control system may be used to discover safer medicines for pain.
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