KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion

J Headache Pain. 2016 Dec;17(1):64. doi: 10.1186/s10194-016-0654-5. Epub 2016 Jul 5.

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.

Findings: 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.

Keywords: Complete Freund’s Adjuvant; Dura mater; IL-1β; KYNA; Trigeminal ganglion; pERK1/2.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Freund's Adjuvant / toxicity*
  • Gene Expression Regulation
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / biosynthesis*
  • Kynurenic Acid / analogs & derivatives*
  • Kynurenic Acid / pharmacology
  • Kynurenic Acid / therapeutic use
  • MAP Kinase Signaling System / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Trigeminal Ganglion / drug effects
  • Trigeminal Ganglion / metabolism*
  • Trigeminal Ganglion / pathology

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, rat
  • Interleukin-1beta
  • SZR 72
  • Freund's Adjuvant
  • Kynurenic Acid