Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-κB nuclear signalling in dorsal root ganglia
| Autor: | Daniele Piomelli, Roberto Russo, Giovanna La Rana, Giuseppe D'Agostino, Anna Iacono, Antonio Calignano, Rosaria Meli, Emanuela Esposito, Salvatore Cuzzocrea, Oscar Sasso, Jesse LoVerme, Giuseppina Mattace Raso |
|---|---|
| Přispěvatelé: | D'Agostino, Giuseppe, LA RANA, Giovanna, Russo, Roberto, O., Sasso, A., Iacono, E., Esposito, MATTACE RASO, Giuseppina, S., Cuzzocrea, J., Loverme, D., Piomelli, Meli, Rosaria, Calignano, Antonio |
| Rok vydání: | 2009 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Central nervous system Nitric Oxide Synthase Type II Pain Palmitic Acids Sciatic nerve Carrageenan Mice chemistry.chemical_compound Ganglia Spinal Internal medicine medicine Animals Ethanolamide PPAR alpha Cell Nucleus Inflammation Pharmacology Analgesics Palmitoylethanolamide Acylethanolamide biology Phenylurea Compounds NF-kappa B Lipid metabolism Peroxisome proliferator-activated receptor Amides Endocannabinoid system Nitric oxide synthase Butyrates medicine.anatomical_structure Endocrinology chemistry Cyclooxygenase 2 Ethanolamines Hyperalgesia Enzyme Induction biology.protein medicine.symptom Endocannabinoids Signal Transduction |
| Zdroj: | D'Agostino, G; La Rana, G; Russo, R; Sasso, O; Iacono, A; Esposito, E; et al.(2009). Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-κB nuclear signalling in dorsal root ganglia. European Journal of Pharmacology, 613(1-3), 54-59. doi: 10.1016/j.ejphar.2009.04.022. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/59q0h2cg |
| ISSN: | 0014-2999 |
| Popis: | Despite the clear roles played by peroxisome proliferators-activated receptor alpha (PPAR-alpha) in lipid metabolism, inflammation and feeding, the effects of its activation in the central nervous system (CNS) are largely unknown. Palmitoylethanolamide (PEA), a member of the fatty-acid ethanolamide family, acts peripherally as an endogenous PPAR-alpha agonist, exerting analgesic and anti-inflammatory effects. Both PPAR-alpha and PEA are present in the CNS, but the specific functions of this lipid and its receptor remain to be clarified. Using the carrageenan-induced paw model of hyperalgesia in mice, we report here that intracerebroventricular administration of PEA (0.1-1 microg) 30 min before carrageenan injection markedly reduced mechanical hyperalgesia up to 24 h following inflammatory insult. This effect was mimicked by GW7647 (1 microg), a synthetic PPAR-alpha agonist. The obligatory role of PPAR-alpha in mediating PEA's actions was confirmed by the lack of anti-hyperalgesic effects in mutant mice lacking PPAR-alpha. PEA significantly reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in sciatic nerves and restored carrageenan-induced reductions of PPAR-alpha in the L4-L6 dorsal root ganglia (DRG). To investigate the mechanism by which PEA attenuated hyperalgesia, we evaluated inhibitory kB-alpha (IkB-alpha) degradation and p65 nuclear factor kB (NF-kappaB) activation in DRG. PEA prevented IkB-alpha degradation and p65 NF-kappaB nuclear translocation, confirming the involvement of this transcriptional factor in the control of peripheral hyperalgesia. These results add further support to the broad-spectrum of biological and pharmacological effects induced by PPAR-alpha agonists, suggesting a centrally mediated component for these drugs in controlling inflammatory pain. |
| Databáze: | OpenAIRE |
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