Abstract
BackgroundNeurogenic 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.MethodsInflammation 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.FindingsPretreatment 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.ConclusionsThis 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.
Highlights
Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology
Basic studies of Neurogenic inflammation (NI) show that it is characterized by proinflammatory responses, caused by the stimulation of peripheral terminals of the primary sensory neurons located in the trigeminal ganglion [2], involved in sensitization and allodynia
PERK1/2 As described earlier [12], pERK1/2 immunoreactivity was detected in a few nuclei of the neurons, including nucleoli, in fresh animals
Summary
Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. 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. Despite growing interest on the role of neuro-immune interactions in migraine, studies show controversial results regarding serum cytokine levels [3,4,5]. One of the first studies demonstrating that the kynurenine pathway has a central role in migraine, was performed by Knyihár-Csillik and coworkers, revealed that electrical stimulation of the trigeminal ganglion decreased kynurenine-aminotransferase immunoreactivity in rat dura mater [8]. Recent studies strengthen the importance of the kynurenine system in case of primary headaches, showing significant reduction in levels kynurenic acid in patients with chronic migraine [9,10,11]
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