Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 54-59 |
| Number of pages | 6 |
| Journal | European Journal of Pharmacology |
| Volume | 613 |
| Issue number | 1-3 |
| Early online date | 20 Apr 2009 |
| DOIs | |
| Publication status | Published - 24 Jun 2009 |
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Keywords
- analgesics
- animals
- butyrates
- carrageenan
- cell nucleus
- central nervous system
- cyclooxygenase 2
- endocannabinoids
- enzyme induction
- ethanolamines
- ganglia, spinal
- hyperalgesia
- male
- mice
- NF-kappa B
- nitric oxide synthase type II
- PPAR alpha
- palmitic acids
- phenylurea compounds
- sciatic nerve
- signal transduction
Cite this
Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-κB nuclear signalling in dorsal root ganglia. / D'Agostino, Giuseppe; La Rana, Giovanna; Russo, Roberto; Sasso, Oscar; Iacono, Anna; Esposito, Emanuela; Mattace Raso, Giuseppina; Cuzzocrea, Salvatore; LoVerme, Jesse; Piomelli, Daniele; Meli, Rosaria; Calignano, Antonio.
In: European Journal of Pharmacology, Vol. 613, No. 1-3, 24.06.2009, p. 54-59.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-κB nuclear signalling in dorsal root ganglia
AU - D'Agostino, Giuseppe
AU - La Rana, Giovanna
AU - Russo, Roberto
AU - Sasso, Oscar
AU - Iacono, Anna
AU - Esposito, Emanuela
AU - Mattace Raso, Giuseppina
AU - Cuzzocrea, Salvatore
AU - LoVerme, Jesse
AU - Piomelli, Daniele
AU - Meli, Rosaria
AU - Calignano, Antonio
PY - 2009/6/24
Y1 - 2009/6/24
N2 - 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.
AB - 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.
KW - analgesics
KW - animals
KW - butyrates
KW - carrageenan
KW - cell nucleus
KW - central nervous system
KW - cyclooxygenase 2
KW - endocannabinoids
KW - enzyme induction
KW - ethanolamines
KW - ganglia, spinal
KW - hyperalgesia
KW - male
KW - mice
KW - NF-kappa B
KW - nitric oxide synthase type II
KW - PPAR alpha
KW - palmitic acids
KW - phenylurea compounds
KW - sciatic nerve
KW - signal transduction
U2 - 10.1016/j.ejphar.2009.04.022
DO - 10.1016/j.ejphar.2009.04.022
M3 - Article
C2 - 19386271
VL - 613
SP - 54
EP - 59
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -