Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury

Tiziana Genovese, Emanuela Esposito, Emanuela Mazzon, Rosanna Di Paola, Rosaria Meli, Placido Bramanti, Daniele Piomelli, Antonio Calignano, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

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 T 5-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.

Original languageEnglish
Pages (from-to)12-23
Number of pages12
JournalJournal of Pharmacology and Experimental Therapeutics
Volume326
Issue number1
DOIs
Publication statusPublished - Jul 2008

ASJC Scopus subject areas

  • Pharmacology

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