Abstract

Background

The neurochemical background of the evolution of headache disorders, still remains partially undiscovered. Accordingly, our aim was to further explore the neurochemical profile of Complete Freund’s adjuvant (CFA)-induced orofacial pain, involving finding the shift point regarding small molecule neurotransmitter concentrations changes vs. that of the previously characterized headache-related neuropeptides. The investigated neurotransmitters consisted of glutamate, γ-aminobutyric acid, noradrenalin and serotonin. Furthermore, in light of its influence on glutamatergic neurotransmission, we measured the level of kynurenic acid (KYNA) and its precursors in the kynurenine (KYN) pathway (KP) of tryptophan metabolism.

Methods

The effect of CFA was evaluated in male Sprague Dawley rats. Animals were injected with CFA (1 mg/ml, 50 μl/animal) into the right whisker pad. We applied high-performance liquid chromatography to determine the concentrations of the above-mentioned compounds from the trigeminal nucleus caudalis (TNC) and somatosensory cortex (ssCX) of rats. Furthermore, we measured some of these metabolites from the cerebrospinal fluid and plasma as well. Afterwards, we carried out permutation t-tests as post hoc analysis for pairwise comparison.

Results

Our results demonstrated that 24 h after CFA treatment, the level of glutamate, KYNA and that of its precursor, KYN was still elevated in the TNC, all diminishing by 48 h. In the ssCX, significant concentration increases of KYNA and serotonin were found.

Conclusion

This is the first study assessing neurotransmitter changes in the TNC and ssCX following CFA treatment, confirming the dominant role of glutamate in early pain processing and a compensatory elevation of KYNA with anti-glutamatergic properties. Furthermore, the current findings draw attention to the limited time interval where medications can target the glutamatergic pathways.

Details

Title
Neurotransmitter and tryptophan metabolite concentration changes in the complete Freund’s adjuvant model of orofacial pain
Author
Cseh, Edina K 1 ; Veres Gábor 2 ; Körtési Tamás 1 ; Polyák Helga 1 ; Nikolett, Nánási 1 ; Tajti János 1 ; Párdutz Árpád 1 ; Klivényi Péter 1 ; Vécsei László 2 ; Zádori Dénes 1 

 University of Szeged, Department of Neurology, Interdisciplinary Excellence Center, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, Szeged, Hungary (GRID:grid.9008.1) (ISNI:0000 0001 1016 9625) 
 University of Szeged, Department of Neurology, Interdisciplinary Excellence Center, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, Szeged, Hungary (GRID:grid.9008.1) (ISNI:0000 0001 1016 9625); MTA-SZTE Neuroscience Research Group, Szeged, Hungary (GRID:grid.9008.1) 
Publication year
2020
Publication date
Dec 2020
Publisher
Springer Nature B.V.
ISSN
11292369
e-ISSN
11292377
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2392891400
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.