ArticleThe journal of headache and pain2020
Neurotransmitter and tryptophan metabolite concentration changes in the complete Freund's adjuvant model of orofacial pain.
Article in The journal of headache and pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 23 citations in OpenAlex.
- Trial
- Pharmacological Modulation of the Kynurenine Pathway Using PF-04859989 Modulates PACAP Signaling in Migraine-Relevant Trigeminal Sensitization.Biomolecules · 2026Article
- Causal relationship between plasma metabolites and chronic regional pain: a Mendelian randomization study.Metabolism open · 2026Article
- Characterization of acupuncture on central amino acid metabolism based on targeted neurotransmitter analysis in mice with inflammatory pain.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Altered aminoacid and lipid metabolism in a rat orofacial inflammation model determined by omics approach: potential role in trigeminal sensitisation.The journal of headache and pain · 2025Article
- Decoding chronic pain: the glutamate-GABA tug of war in the cerebral cortex.Frontiers in molecular neuroscience · 2025Review
- The role of kynurenines in migraine-related neuroimmune pathways.The journal of headache and pain · 2024Review
- Ion Channel Disturbances in Migraine Headache: Exploring the Potential Role of the Kynurenine System in the Context of the Trigeminovascular System.International journal of molecular sciences · 2023Review
- Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions.Cells · 2023Review
- Cluster headache and kynurenines.The journal of headache and pain · 2023Article
- Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings.International journal of molecular sciences · 2023Review
- Transcriptional Alterations of Mouse Trigeminal Ganglion Neurons Following Orofacial Inflammation Revealed by Single-Cell Analysis.Frontiers in cellular neuroscience · 2022Article
- Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period.The journal of headache and pain · 2021Article
- The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents.International journal of molecular sciences · 2020Review
- Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.Molecular painReview
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10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe 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.
methodsThe 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.
resultsOur 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.
conclusionThis 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.
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