title: Implication of allopregnanolone in the antinociceptive effect of N-palmitoylethanolamide in acute or persistent pain.
abstract: 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.
authors: 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.
authors: Oscar
authors: O
authors: Sasso
authors: Roberto
authors: R
authors: Russo
authors: Sergio
authors: S
authors: Vitiello
authors: Giuseppina Mattace
authors: GM
authors: Raso
authors: Giuseppe
authors: G
authors: D'Agostino
authors: Anna
authors: A
authors: Iacono
authors: Giovanna
authors: G
authors: La Rana
authors: Monique
authors: M
authors: Vallée
authors: Salvatore
authors: S
authors: Cuzzocrea
authors: Pier Vincenzo
authors: PV
authors: Piazza
authors: Rosaria
authors: R
authors: Meli
authors: Antonio
authors: A
authors: Calignano
mesh_terms: D000577:Amides; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D063388:Endocannabinoids; D004983:Ethanolamines; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement; D010169:Palmitic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D011280:Pregnanolone / Q000096:biosynthesis*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000577:Amides; D000700:Analgesics; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; C005958:palmidrol; D011280:Pregnanolone