Characterisation of peroxisome proliferator-activated receptor signalling in the midbrain periaqueductal grey of rats genetically prone to heightened stress, negative affect and hyperalgesia

The stress-hyperresponsive Wistar-Kyoto (WRY) rat strain exhibits a hyperalgesic phenotype and is a useful genetic model for studying stress-pain interactions. Peroxisome proliferator-activated receptor (PPAR) signalling in the midbrain periaqueductal grey (PAG) modulates pain. This study characterised PPAR signalling in the PAG of WRY rats exposed to the formalin test of inflammatory pain, versus Sprague-Dawley (SD) controls.Formalin injection reduced levels of the endogenous PPAR ligands N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) in the lateral(1) PAG of SD rats, but not WRY rats which exhibited higher levels of these analytes compared with formalin-injected SD counterparts. Levels of mRNA coding for fatty acid amide hydrolase (FAAH; catabolises PEA and OEA) were lower in the]PAG of WRY versus SD rats. PPARy mRNA and protein levels in the IPAG were higher in saline-treated WRY rats, with PPARy protein levels reduced by formalin treatment in WRY rats only. In the dorsolateral(dl) or ventrolateral(v1) PAG, there were no effects of formalin injection on PEA or OEA levels but there were some differences in levels of these analytes between saline-treated WRY and SD rats and some formalin-evoked alterations in levels of PPARy, PPARy or FAAH mRNA in WKY and/or SD rats. Pharmacological blockade of PPARy in the IPAG enhanced formalin-evoked nociceptive behaviour in WRY, but not SD, rats.These data indicate differences in the PPAR signalling system in the PAG of WRY versus SD rats and suggest that enhanced PEA/OEA-mediated tone at PPARy in the IPAG may represent an adaptive mechanism to lower hyperalgesia in WRY rats. (C) 2016 Elsevier B.V. All rights reserved.This work was funded by grants from Science Foundation Ireland (10/IN.1/B2976), The Irish Research Council, CNPq - Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil (207530/2014-9) and the National University of Ireland Galway