title: A role for PPARα in the medial prefrontal cortex in formalin-evoked nociceptive responding in rats.
abstract: OBJECTIVE
  The nuclear hormone receptor, PPARα, and its endogenous ligands, are involved in pain modulation. PPARα is expressed in the medial prefrontal cortex (mPFC), a key brain region involved in both the cognitive-affective component of pain and in descending modulation of pain. However, the role of PPARα in the mPFC in pain responding has not been investigated. Here, we investigated the effects of pharmacological modulation of PPARα in the rat mPFC on formalin-evoked nociceptive behaviour and the impact of formalin-induced nociception on components of PPARα signalling in the mPFC.
  
  
  METHODS
  The effects of intra-mPFC microinjection of a PPARα agonist (GW7647) or a PPARα antagonist (GW6471) on formalin-evoked nociceptive behaviour in rats were studied. Quantitative real-time PCR and LC-MS/MS were used to study the effects of intraplantar injection of formalin on PPARα mRNA expression and levels of endogenous ligands, respectively, in the mPFC.
  
  
  RESULTS
  Intra-mPFC administration of GW6471, but not GW7647, resulted in delayed onset of the early second phase of formalin-evoked nociceptive behaviour. Furthermore, formalin-evoked nociceptive behaviour was associated with significant reductions in mPFC levels of endogenous PPARα ligands (N-palmitoylethanolamide and N-oleoylethanolamide) and a 70% reduction in PPARα mRNA but not protein expression.
  
  
  CONCLUSIONS
  These data suggest that endogenous ligands may act at PPARα in the mPFC to play a facilitatory/permissive role in second phase formalin-evoked nociceptive behaviour in rats.
  
  
  BACKGROUND
  This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, National University of Ireland Galway, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, Galway, Ireland.
authors.forename: B N
authors.initials: BN
authors.lastname: Okine
authors.forename: K
authors.initials: K
authors.lastname: Rea
authors.forename: W M
authors.initials: WM
authors.lastname: Olango
authors.forename: J
authors.initials: J
authors.lastname: Price
authors.forename: S
authors.initials: S
authors.lastname: Herdman
authors.forename: M K
authors.initials: MK
authors.lastname: Madasu
authors.forename: M
authors.initials: M
authors.lastname: Roche
authors.forename: D P
authors.initials: DP
authors.lastname: Finn
mesh_terms: D000818:Animals; D005557:Formaldehyde / Q000008:administration & dosage*; D008297:Male; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D010146:Pain / Q000139:chemically induced*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047493:PPAR alpha; D005557:Formaldehyde
keywords: GW6471; GW7647; N-oleoylethanolamide; N-palmitoylethanolamide; PPARα; Sprague-Dawley rats; formalin test; medial prefrontal cortex; pain