Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH:
Allodynia was induced by intraplantar injection of LPS. Complementary genetic and pharmacological approaches were used to determine the strategy of blocking FAAH to reverse LPS-induced allodynia. Endocannabinoid levels were quantified using mass spectroscopy analyses. KEY RESULTS: FAAH (-/-) mice or wild-type mice treated with FAAH inhibitors ( URB597, OL-135 and PF-3845) displayed an anti-allodynic phenotype. Furthermore, i.p. PF-3845 increased AEA levels in the brain and spinal cord. Additionally, intraplantar PF-3845 produced a partial reduction in allodynia. However, the anti-allodynic phenotype was absent in mice expressing FAAH exclusively in the nervous system under a neural specific enolase promoter, implicating the involvement of neuronal fatty acid amides (FAAs). The anti-allodynic effects of FAAH-compromised mice required activation of both CB1 and CB2 receptors, but other potential targets of FAA substrates (i.e. µ- opioid, TRPV1 and PPARα receptors) had no apparent role. CONCLUSIONS AND IMPLICATIONS: LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
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Authors | Lamont Booker, Steven G Kinsey, Rehab A Abdullah, Jacqueline L Blankman, Jonathan Z Long, Cyrine Ezzili, Dale L Boger, Benjamin F Cravatt, Aron H Lichtman |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 165
Issue 8
Pg. 2485-96
(Apr 2012)
ISSN: 1476-5381 [Electronic] England |
PMID | 21506952
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Chemical References |
- Arachidonic Acids
- Endocannabinoids
- Enzyme Inhibitors
- Glycerides
- Lipopolysaccharides
- PF 3845
- Piperidines
- Polyunsaturated Alkamides
- Pyridines
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- glyceryl 2-arachidonate
- Amidohydrolases
- fatty-acid amide hydrolase
- anandamide
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Topics |
- Amidohydrolases
(antagonists & inhibitors, deficiency, genetics)
- Animals
- Arachidonic Acids
(metabolism)
- Brain
(drug effects, metabolism)
- Endocannabinoids
- Enzyme Inhibitors
(pharmacology, therapeutic use)
- Female
- Glycerides
(metabolism)
- Hyperalgesia
(chemically induced, drug therapy, metabolism)
- Inflammation
(chemically induced, drug therapy, metabolism)
- Lipopolysaccharides
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Peripheral Nervous System
(drug effects, metabolism)
- Piperidines
(pharmacology, therapeutic use)
- Polyunsaturated Alkamides
(metabolism)
- Pyridines
(pharmacology, therapeutic use)
- Receptor, Cannabinoid, CB1
(metabolism)
- Receptor, Cannabinoid, CB2
(metabolism)
- Spinal Cord
(drug effects, metabolism)
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