A role for PPARa in the medial prefrontal cortex in formalin- evoked nociceptive responding in rats

Background and PurposeThe nuclear hormone receptor, PPAR, and its endogenous ligands, are involved in pain modulation. PPAR 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 PPAR in the mPFC in pain responding has not been investigated. Here, we investigated the effects of pharmacological modulation of PPAR in the rat mPFC on formalin-evoked nociceptive behaviour and the impact of formalin-induced nociception on components of PPAR signalling in the mPFC. Experimental ApproachThe effects of intra-mPFC microinjection of a PPAR agonist (GW7647) or a PPAR 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 PPAR mRNA expression and levels of endogenous ligands, respectively, in the mPFC. Key ResultsIntra-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 PPAR ligands (N-palmitoylethanolamide and N-oleoylethanolamide) and a 70% reduction in PPAR mRNA but not protein expression. Conclusions and ImplicationsThese data suggest that endogenous ligands may act at PPAR in the mPFC to play a facilitatory/permissive role in second phase formalin-evoked nociceptive behaviour in rats. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit