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

Lukács, M. LU ; Warfvinge, K. LU ; Kruse, L. S.; Tajti, J.; Fülöp, F.; Toldi, J.; Vécsei, L. and Edvinsson, L. LU (2016) In Journal of Headache and Pain 17(1).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Complete Freund’s Adjuvant, Dura mater, IL-1β, KYNA, pERK1/2, Trigeminal ganglion
in
Journal of Headache and Pain
volume
17
issue
1
publisher
Springer
external identifiers
  • scopus:84977575572
  • wos:000386608100002
ISSN
1129-2369
DOI
10.1186/s10194-016-0654-5
language
English
LU publication?
yes
id
a09d598e-2659-469d-941e-03cd661f081c
date added to LUP
2016-10-12 13:22:06
date last changed
2017-04-09 04:50:30
@article{a09d598e-2659-469d-941e-03cd661f081c,
  abstract     = {<p>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.</p>},
  articleno    = {64},
  author       = {Lukács, M. and Warfvinge, K. and Kruse, L. S. and Tajti, J. and Fülöp, F. and Toldi, J. and Vécsei, L. and Edvinsson, L.},
  issn         = {1129-2369},
  keyword      = {Complete Freund’s Adjuvant,Dura mater,IL-1β,KYNA,pERK1/2,Trigeminal ganglion},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Springer},
  series       = {Journal of Headache and Pain},
  title        = {KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion},
  url          = {http://dx.doi.org/10.1186/s10194-016-0654-5},
  volume       = {17},
  year         = {2016},
}