Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund’s Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72.
Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord.
We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration.
This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.
Global Burden of Disease Study 2013 Collaborators. Global (2015) regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386(9995):743–800
Noseda R, Burstein R, (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain 154(Suppl1):1–21
Fulop F, Szatmari I, Toldi J, Vecsei L (2012) Modifications on the carboxylic function of kynurenic acid. J Neural Transm (Vienna) 119(2):109–114 CrossRef
Kaszaki J, Erces D, Varga G, Szabo A, Vecsei L, Boros M (2012) Kynurenines and intestinal neurotransmission: the role of N-methyl-D-aspartate receptors. J Neural Transm (Vienna) 119(2):211–223 CrossRef
Eftekhari S, Salvatore CA, Johansson S, Chen TB, Zeng Z, Edvinsson L (1600) Localization of CGRP, CGRP receptor PACAP and glutamate in trigeminal ganglion Relation to the blood–brain barrier. Brain Res 2015:93–109
Rozsa E, Robotka H, Vecsei L, Toldi J (2008) The Janus-face kynurenic acid. J Neural Transm (Vienna) 115(8):1087–1091 CrossRef
Fejes-Szabo A, Bohar Z, Vamos E, Nagy-Grocz G, Tar L, Veres G, Zadori D, Szentirmai M, Tajti J, Szatmari I, Fulop F, Toldi J, Pardutz A, Vecsei L (2014) Pre-treatment with new kynurenic acid amide dose-dependently prevents the nitroglycerine-induced neuronal activation and sensitization in cervical part of trigemino-cervical complex. J Neural Transm (Vienna) 121(7):725–738 CrossRef
Knyihar-Csillik E, Toldi J, Mihaly A, Krisztin-Peva B, Chadaide Z, Nemeth H, Fenyo R, Vecsei L (2007) Kynurenine in combination with probenecid mitigates the stimulation-induced increase of c-fos immunoreactivity of the rat caudal trigeminal nucleus in an experimental migraine model. J Neural Transm (Vienna) 114(4):417–421 CrossRef
Aminian O, Eftekhari S, Mazaheri M, Sharifian SA, Sadeghniiat-Haghighi K (2011) Urinary beta2 microglobulin in workers exposed to arc welding fumes. Acta Med Iran 49(11):748–752 PubMed
- Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: attenuated by KYNA derivate (SZR72)
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