RT Journal Article SR Electronic T1 Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 12 OP 23 DO 10.1124/jpet.108.136903 VO 326 IS 1 A1 Tiziana Genovese A1 Emanuela Esposito A1 Emanuela Mazzon A1 Rosanna Di Paola A1 Rosaria Meli A1 Placido Bramanti A1 Daniele Piomelli A1 Antonio Calignano A1 Salvatore Cuzzocrea YR 2008 UL http://jpet.aspetjournals.org/content/326/1/12.abstract AB Activation of peroxisome proliferator-activated receptor (PPAR)-α, a member of the nuclear receptor superfamily, modulates inflammation and tissue injury events associated with spinal cord trauma in mice. Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through a mechanism dependent on PPAR-α activation. The aim of the present study was to evaluate the effect of the PEA on secondary damage induced by experimental spinal cord injury (SCI) in mice. SCI was induced by application of vascular clips to the dura mater via a four-level T5-T8 laminectomy. This resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis. Repeated PEA administration (10 mg/kg i.p.; 30 min before and 1 and 6 h after SCI) significantly reduced: 1) the degree of spinal cord inflammation and tissue injury, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription factor activation-κB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis. Moreover, PEA treatment significantly ameliorated the recovery of motor limb function. Together, the results indicate that PEA reduces inflammation and tissue injury associated with SCI and suggest a regulatory role for endogenous PPAR-α signaling in the inflammatory response associated with spinal cord trauma. The American Society for Pharmacology and Experimental Therapeutics