Implication of allopregnanolone in the antinociceptive effect of N-palmitoylethanolamide in acute or persistent pain
Pain. 2012-01-01; 153(1): 33-41
DOI: 10.1016/j.pain.2011.08.010
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1. Pain. 2012 Jan;153(1):33-41. doi: 10.1016/j.pain.2011.08.010. Epub 2011 Sep 3.
Implication of allopregnanolone in the antinociceptive effect of
N-palmitoylethanolamide in acute or persistent pain.
Sasso O(1), Russo R, Vitiello S, Raso GM, D’Agostino G, Iacono A, La Rana G,
Vallée M, Cuzzocrea S, Piazza PV, Meli R, Calignano A.
Author information:
(1)Department of Experimental Pharmacology, University of Naples “Federico II”,
via D. Montesano 49, 80131 Naples, Italy INSERM U862, Institut F. Magendie,
Bordeaux, France Université de Bordeaux, Bordeaux, France Department of Clinical
and Experimental Medicine and Pharmacology, School of Medicine, University of
Messina, Italy IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy.
Comment in
Pain. 2012 Jan;153(1):3-4.
We investigated the involvement of de novo neurosteroid synthesis in the
mechanisms underlying the analgesic and antihyperalgesic effects of
N-palmitoylethanolamine (PEA) in two models of acute and persistent pain, the
formalin test and carrageenan-induced paw edema. The pivotal role of peroxisome
proliferator-activated receptor (PPAR)-α in the antinocifensive effect of PEA
was confirmed by the lack of this effect in PPAR-α-null mice. PEA
antinociceptive activity was partially reduced when the animals were treated
with aminoglutethimide or finasteride, implying that de novo neurosteroid
synthesis is involved in the effect of PEA. Accordingly, in the spinal cord, the
allopregnanolone (ALLO) levels were increased by PEA treatment both in formalin-
and carrageenan-exposed mice, as revealed by gas chromatography-mass
spectrometry. In agreement with those data, in both pain models, PEA
administration in challenged mice specifically restored the expression of two
proteins involved in neurosteroidogenensis, the steroidogenic acute regulatory
protein (StAR) and cytochrome P450 side-chain cleavage (P450scc) in the
ipsilateral horns of spinal cord, without affecting their expression in the
contralateral side. These results provide new information about the involvement
of de novo neurosteroid synthesis in the modulation of pain behavior by PEA.
Copyright © 2011 International Association for the Study of Pain. Published by
Elsevier B.V. All rights reserved.
DOI: 10.1016/j.pain.2011.08.010
PMID: 21890273 [Indexed for MEDLINE]