Journal
PHARMACOLOGICAL RESEARCH
Volume 97, Issue -, Pages 7-15Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2015.04.001
Keywords
Fatty acid amide hydrolase; Soluble epoxide hydrolase; Fatty acid ethanolamide (FAE); Epoxidized fatty acid (EpFA); Anti-nociception; Acute and chronic pain
Categories
Funding
- National Institutes on Drug Abuse [R01-DA-012413, DP1DA031387]
- National Institute of Environmental Health Sciences (NIEHS) [R01 ES002710]
- NIEHS Superfund Research Program [P42 ES004699]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R21AR062866]
- National Institute of Neurological Disorders and Stroke (NINDS) [U54 NS079202-01]
- [NIEHS T32ES007059]
- [NIH 5T32DC008072-05]
Ask authors/readers for more resources
We need better medicines to control acute and chronic pain. Fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) catalyze the deactivating hydrolysis of two classes of bioactive lipid mediators - fatty acid ethanolamides (FAEs) and epoxidized fatty acids (EpFAs), respectively - which are biogenetically distinct but share the ability to attenuate pain responses and inflammation. In these experiments, we evaluated the antihyperalgesic activity of small-molecule inhibitors of FAAH and sEH, administered alone or in combination, in two pain models: carrageenan-induced hyperalgesia in mice and streptozocin-induced allodynia in rats. When administered separately, the sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea (TPPU) and the peripherally restricted FAAH inhibitor URB937 were highly active in the two models. The combination TPPU plus URB937 was markedly synergistic, as assessed using isobolographic analyses. The results of these experiments reveal the existence of a possible functional crosstalk between FAEs and EpFAs in regulating pain responses. Additionally, the results suggest that combinations of sEH and FAAH inhibitors might be exploited therapeutically to achieve greater analgesic efficacy. (c) 2015 Elsevier Ltd. All rights reserved.
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