title: Characterisation of peroxisome proliferator-activated receptor signalling in the midbrain periaqueductal grey of rats genetically prone to heightened stress, negative affect and hyperalgesia.
abstract: The stress-hyperresponsive Wistar-Kyoto (WKY) 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 WKY 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(l) PAG of SD rats, but not WKY 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 lPAG of WKY versus SD rats. PPARγ mRNA and protein levels in the lPAG were higher in saline-treated WKY rats, with PPARγ protein levels reduced by formalin treatment in WKY rats only. In the dorsolateral(dl) or ventrolateral(vl) 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 WKY and SD rats and some formalin-evoked alterations in levels of PPARα, PPARγ or FAAH mRNA in WKY and/or SD rats. Pharmacological blockade of PPARγ in the lPAG enhanced formalin-evoked nociceptive behaviour in WKY, but not SD, rats. These data indicate differences in the PPAR signalling system in the PAG of WKY versus SD rats and suggest that enhanced PEA/OEA-mediated tone at PPARγ in the lPAG may represent an adaptive mechanism to lower hyperalgesia in WKY rats.
authors.affiliation: Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Bright N
authors.initials: BN
authors.lastname: Okine
authors.affiliation: Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Gaspar
authors.affiliation: Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Madasu
authors.affiliation: Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Weredeselam M
authors.initials: WM
authors.lastname: Olango
authors.affiliation: Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Harhen
authors.affiliation: Physiology, School of Medicine, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Roche
authors.affiliation: Pharmacology and Therapeutics, Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland; Galway Neuroscience Centre and Centre for Pain Research, NCBES, National University of Ireland Galway, University Road, Galway, Ireland. Electronic address: david.finn@nuigalway.ie.
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
mesh_terms: D000339:Affect / Q000502:physiology; D000818:Animals; D003863:Depression / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D059226:Nociceptive Pain / Q000378:metabolism; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological; D015398:Signal Transduction; D013045:Species Specificity; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors
keywords: Descending pain pathway; Formalin; N-oleoylethanolamide (OEA); N-palmitoylethanolamide (PEA); Peroxisome proliferator-activated receptor (PPAR); Wistar-Kyoto (WKY)