title: KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion.
abstract: BACKGROUND
  Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion.
  
  
  METHODS
  Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot.
  
  
  RESULTS
  Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose.
  
  
  CONCLUSIONS
  This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.
authors.affiliation: Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.|Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Lukács
authors.affiliation: Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden. karin.warfvinge@med.lu.se.|Department of Clinical Experimental Research, Copenhagen University, Glostrup Hospital, Copenhagen, Denmark. karin.warfvinge@med.lu.se.|Department of Medicine, Institute of Clinical Sciences, Lund University, Sölvegatan 17, SE 221 84, Lund, Sweden. karin.warfvinge@med.lu.se.
authors.forename: K
authors.identifier: http://orcid.org/0000-0002-1356-8725
authors.initials: K
authors.lastname: Warfvinge
authors.affiliation: Department of Clinical Experimental Research, Copenhagen University, Glostrup Hospital, Copenhagen, Denmark.
authors.forename: L S
authors.initials: LS
authors.lastname: Kruse
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Tajti
authors.affiliation: Institute of Pharmaceutical Chemistry and MTA-SZTE Research Group for Stereochemistry, University of Szeged, Szeged, Hungary.
authors.forename: F
authors.initials: F
authors.lastname: Fülöp
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.|MTA SZTE Neuroscience Research Group, Szeged, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Toldi
authors.affiliation: Department of Neurology, University of Szeged, Szeged, Hungary.|MTA SZTE Neuroscience Research Group, Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.|Department of Clinical Experimental Research, Copenhagen University, Glostrup Hospital, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005620:Freund's Adjuvant / Q000633:toxicity*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; C533052:SZR 72; D005620:Freund's Adjuvant; D007736:Kynurenic Acid
keywords: Complete Freund’s Adjuvant; Dura mater; IL-1β; KYNA; Trigeminal ganglion; pERK1/2