A role for PPARα in the medial prefrontal cortex in formalin‐evoked nociceptive responding in rats. (March 2014)

• Record Type: Journal Article
• Authors: Okine, B N; Rea, K; Olango, W M; Price, J; Herdman, S; Madasu, M K; Roche, M; Finn, D P
• Is Part Of: British journal of pharmacology. Volume 171:Number 6(2014:Mar.)
• Page Start: 1462
• Page End: 1471
• Publication Date: 2014-03
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12540
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12540-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>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.</p> </sec> <sec id="bph12540-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>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.</p> </sec> <sec id="bph12540-sec-0003" sec-type="section"> <title>Key Results</title> <p>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 (<italic>N</italic>‐palmitoylethanolamide and <italic>N</italic>‐oleoylethanolamide) and a 70% reduction in PPARα mRNA but not protein expression.</p> </sec> <sec id="bph12540-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>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.</p> </sec> <sec id="bph12540-sec-5001" sec-type="relatedArticles"> <title>Linked Articles</title> <p>This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit <ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">http://dx.doi.org/10.1111/bph.2014.171.issue‐6</ext-link></p> </sec> </abstract>