The effects of certain TRP channels and voltage-gated KCNQ/Kv7 channel opener retigabine on calcitonin gene-related peptide release in the trigeminovascular system

Citak, Arzu; Kılınç, Erkan; Torun, İbrahim Ethem; Ankarali, Seyit; Dağıstan, Yaşar; Yoldaş, Hamit

doi:10.1177/03331024221114773

Cited by 14 publications

(11 citation statements)

References 48 publications

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“…A high prevalence of migraine was reported in individuals with certain mtDNA mutations 10,26 . Preclinical studies also demonstrated the activation of transient receptor potential ankyrin‐1 (TRPA1) in meningeal trigeminal nociceptors by reactive oxygen and nitrogen species (ROS/NOS), leading to neurogenic vasodilatation and CGRP release 21,27,28 …”

Section: Discussionmentioning

confidence: 99%

“…Measurement of serum concentrations of peptides was carried out using the enzyme‐linked immunosorbent assay (ELISA) method, which has worldwide validity and reliability. Briefly, the measurements were performed as previously described by us and other groups 19–21 . HIF‐1α, FGF‐21, and GDF‐15 ELISA kits were purchased from Elabscience and CGRP, PACAP‐38, VIP, and SP ELISA kits from BT LAB.…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, the measurements were performed as previously described by us and other groups. [19][20][21] HIF-1α, FGF-21, and GDF-15 ELISA kits were purchased from Elabscience and CGRP, PACAP-38, VIP, and SP ELISA kits from BT LAB. The detection limit was 37.5 pg/mL for HIF-1α, 18.75 pg/mL for FGF-21, 14.06 pg/ mL for GDF-15, 1.12 pg/mL for CGRP, 11.53 pg/mL for PACAP-38, 3.11 pg/mL for VIP, and 2.39 pg/mL for SP.…”

Section: Determination Of Serum Levels Of the Peptidesmentioning

confidence: 99%

“…CGRP, calcitonin gene-related peptide; FGF-21, fibroblast growth factor-21; GDF-15, growth differentiation factor-15; HIF-1α, hypoxia inducible factor-1α; PACAP-38, pituitary adenylate cyclase-activating peptide-38; ROC, receiver operating characteristic; SP, substance P; VIP, vasoactive intestinal peptide. [Color figure can be viewed at wileyonlinelibrary.com] transient receptor potential ankyrin-1 (TRPA1)in meningeal trigeminal nociceptors by reactive oxygen and nitrogen species (ROS/NOS), leading to neurogenic vasodilatation and CGRP release 21,27,28. Serum concentrations of FGF-21 and GDF-15 were recently studied in adult migraine patients,20,29 with inconsistent results.Therefore, we aimed to study a more homogeneous group: (i) we recruited only pediatric patients with migraine without aura; (ii) the sex of the pediatric patients with migraine in our study was solely female; and (iii) the patients were not using any medications, including prophylactic migraine medication.…”

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confidence: 99%

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Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

Kilinc,

Danis

et al. 2023

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ObjectiveThe purpose of this study was to investigate the serum levels of mitochondrial metabolism/reactive oxygen species (ROS)–related peptides (hypoxia inducible factor‐1α [HIF‐1α], fibroblast growth factor‐21 [FGF‐21], growth differentiation factor‐15 [GDF‐15]) and key migraine‐related neuropeptides (calcitonin gene–related peptide [CGRP], pituitary adenylate cyclase‐activating peptide‐38 [PACAP‐38], substance P [SP], and vasoactive intestinal peptide [VIP]) during migraine attacks and to evaluate their diagnostic value in pediatric migraine.BackgroundThere is increasing evidence for the important role of impairment in oxidative mitochondrial metabolism in the pathophysiology of migraine. Potential biomarkers that may reflect the relationship between migraine and mitochondrial dysfunction are unclear.MethodsA total of 68 female pediatric migraine patients without aura and 20 female healthy controls aged 8–18 years, admitted to the hospital, were enrolled in this cross‐sectional study. Serum concentrations of these molecules were determined by enzyme‐linked immunosorbent assays, and clinical features and their possible diagnostic value were analyzed.ResultsSerum levels of HIF‐1α (252.4 ± 51.9 [mean ± standard deviation]) pg/mL), GDF‐15 (233.7 ± 24.7 pg/mL), FGF‐21 (96.1 ± 13.1 pg/mL), CGRP (44.5 ± 11.3), and PACAP‐38 (504.7 ± 128.9) were significantly higher in migraine patients compared to healthy controls (199.8 ± 26.8, 192.8 ± 20.7, 79.3 ± 4.1, 34.1 ± 3.5 and 361.2 ± 86.3 pg/mL, respectively). The serum levels of these peptides were also higher in patients with chronic migraine than in patients with episodic migraine, and higher in the ictal period than in the interictal period. A positive correlation was found between attack frequency and both HIF‐1α and FGF‐21 levels in migraine patients. Serum levels of VIP and SP were not different between the migraine patients and healthy controls.ConclusionMigraine attacks are accompanied by elevated HIF‐1α, FGF‐21, GDF‐15, CGRP, and PACAP‐38 in medication‐naive pediatric patients with migraine. Elevated circulating mitochondrial metabolism/ROS‐related peptides suggest a mitochondrial stress in pediatric migraine attacks and may have potential diagnostic value in monitoring disease progression and treatment response in children. Novel approaches intervening with mitochondrial metabolism need to be investigated.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Determination Of Serum Levels Of the Peptidesmentioning

confidence: 99%

mentioning

confidence: 99%

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Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

Kilinc,

Danis

et al. 2023

Headache

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“…), the whole animal was transcardially perfused with 200 mL of phosphate‐buffered saline (pH: 7.4) through a cannula inserted into the left ventricle. Immediately after, cranial dura mater, brainstem trigeminal nucleus caudalis (TNC) and trigeminal ganglia were gently harvested as previously described by us and other groups (Citak et al, 2022; Kilinc et al, 2017; Labastida‐Ramírez et al, 2020; Rasmussen et al, 2022). Briefly, after the head was cut, the cranium was cleared of the scalp and other tissues.…”

Section: Methodsmentioning

confidence: 99%

D2 dopamine receptor‐mediated mechanisms of dopaminergic system modulation in in vivo and in vitro experimental models of migraine

Kılınc

Torun

Kılınç

2023

Eur J of Neuroscience

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The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of dopaminergic system modulation in the in vivo and in vitro rat models of migraine. Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol and 5‐HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin‐induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal calcitonin gene‐related peptide (CGRP) release in vitro hemiskull preparations. Mechanical allodynia was tested by von Frey filaments. CGRP concentrations in trigeminovascular structures and in vitro superfusates and c‐Fos levels in the brainstem were determined by enzyme‐linked immunosorbent assay. Meningeal mast cells were evaluated with toluidine blue staining. Apomorphine further enhanced nitroglycerin‐induced mechanical allodynia, brainstem c‐fos expression, trigeminal ganglion and brainstem CGRP concentrations and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine‐induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine‐ or nitroglycerin‐induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in vitro, whereas the other administrations were ineffective. Apomorphine‐mediated dopaminergic activation exacerbated nitroglycerin‐stimulated nociceptive reactions by further enhancing c‐fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5‐HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine‐related parameters in dopaminergic activation‐ and/or NTG‐induced migraine‐like conditions.

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Capsaicin, The Vanilloid Receptor TRPV1 Agonist in Neuroprotection: Mechanisms Involved and Significance

Abdel-Salam

Mózsik

2023

Neurochem Res

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Hot peppers, also called chilli, chilli pepper, or paprika of the plant genus Capsicum (family Solanaceae), are one of the most used vegetables and spices worldwide. Capsaicin (8-methyl N-vanillyl-6-noneamide) is the main pungent principle of hot green and red peppers. By acting on the capsaicin receptor or transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1), capsaicin selectively stimulates and in high doses defunctionalizes capsaicin-sensitive chemonociceptors with C and Aδ afferent fibers. This channel, which is involved in a wide range of neuronal processes, is expressed in peripheral and central branches of capsaicin-sensitive nociceptive neurons, sensory ganglia, the spinal cord, and different brain regions in neuronal cell bodies, dendrites, astrocytes, and pericytes. Several experimental and clinical studies provided evidence that capsaicin protected against ischaemic or excitotoxic cerebral neuronal injury and may lower the risk of cerebral stroke. By preventing neuronal death, memory impairment and inhibiting the amyloidogenic process, capsaicin may also be beneficial in neurodegenerative disorders such as Parkinson’s or Alzheimer’s diseases. Capsaicin given in systemic inflammation/sepsis exerted beneficial antioxidant and anti-inflammatory effects while defunctionalization of capsaicin-sensitive vagal afferents has been demonstrated to increase brain oxidative stress. Capsaicin may act in the periphery via the vagal sensory fibers expressing TRPV1 receptors to reduce immune oxidative and inflammatory signalling to the brain. Capsaicin given in small doses has also been reported to inhibit the experimentally-induced epileptic seizures. The aim of this review is to provide a concise account on the most recent findings related to this topic. We attempted to delineate such mechanisms by which capsaicin exerts its neuronal protective effects. We also aimed to provide the reader with the current knowledge on the mechanism of action of capsaicin on sensory receptors.

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The effects of certain TRP channels and voltage-gated KCNQ/Kv7 channel opener retigabine on calcitonin gene-related peptide release in the trigeminovascular system

Cited by 14 publications

References 48 publications

Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

D2 dopamine receptor‐mediated mechanisms of dopaminergic system modulation in in vivo and in vitro experimental models of migraine

Capsaicin, The Vanilloid Receptor TRPV1 Agonist in Neuroprotection: Mechanisms Involved and Significance

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