Metoclopramide inhibits trigeminovascular activation:evidence for effective acute attack treatment in migraine

Aydin, Hacer Doğanay; Vurallı, Doğa; Akçali, Didem Tuba; Bolay, Hayrünnisa

doi:10.3906/sag-1601-195

Cited by 16 publications

(11 citation statements)

References 15 publications

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“…Another supporting evidence for the linkage of CSD to head pain came from the drug studies in rodents. Trigeminal activation at the second order neurons in TNC by CSD was reversed by sumatriptan [12, 20], valproic acid [23], topiramate [29], CGRP receptor antagonists [30] or metoclopramide [31]. Latter two agents also significantly reversed the CSD induced pain behavior such as grooming and freezing in addition to reduced von Frey thresholds and cold allodynia in freely moving rodents.…”

Section: What Is the Evidence Linking Csd To Head Pain?mentioning

confidence: 99%

Aura and Head pain: relationship and gaps in the translational models

2019

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Migraine is a complex brain disorder and initiating events for acute attacks still remain unclear. It seems difficult to explain the development of migraine headache with one mechanism and/or a single anatomical location. Cortical spreading depression (CSD) is recognized as the biological substrate of migraine aura and experimental animal studies have provided mechanisms that possibly link CSD to the activation of trigeminal neurons mediating lateralized head pain. However, some CSD features do not match the clinical features of migraine headache and there are gaps in translating CSD to migraine with aura. Clinical features of migraine headache and results from research are critically evaluated; and consistent and inconsistent findings are discussed according to the known basic features of canonical CSD: typical SD limited to the cerebral cortex as it was originally defined. Alternatively, arguments related to the emergence of SD in other brain structures in addition to the cerebral cortex or CSD initiated dysfunction in the thalamocortical network are proposed. Accordingly, including thalamus, particularly reticular nucleus and higher order thalamic nuclei, which functions as a hub connecting the visual, somatosensory, language and motor cortical areas and subjects to modulation by brain stem projections into the CSD theory, would greatly improve our current understanding of migraine.

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Section: What Is the Evidence Linking Csd To Head Pain?mentioning

confidence: 99%

Aura and Head pain: relationship and gaps in the translational models

2019

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“…D2 receptor blockade prevents the prodromal symptoms [ 39 ]. The efficacy of D2 antagonists in the acute treatment of migraine is supported by both clinical and preclinical studies [ 44 – 46 ]. Platelet [ 47 ] and plasma levels of dopamine [ 48 , 49 ] and dopamine metabolite levels in cerebrospinal fluid were higher in migraine patients compared to healthy controls [ 47 ] suggesting an abnormal metabolism of dopamine in migraine [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition

et al. 2022

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Background/aim Certain constituents in migraine food triggers and non-steroidal anti-inflammatory drugs (NSAIDs) inhibit sulfotransferases (SULTs) that detoxify drugs/chemicals and play role in the metabolism of neurotransmitters. We aimed to dissect SULT1A1 modulation of CSD susceptibility and behavior in an in vivo experimental model using hesperidin, a SULT1A1 inhibitor found in citrus fruits (known migraine triggers) and mefenamic acid (SULT1A1 inhibitor), an NSAID to simulate medication overuse. Methods Hesperidin was used as SULT1A1 inhibitor found in citrus fruits, known migraine triggers and mefenamic acid (NSAID), another SULT1A1 inhibitor, was used to induce MO in rats. The groups were; 1) Hesperidin (ip) or its vehicle-DMSO (ip) 2) Chronic (4 weeks) mefenamic acid (ip) or its vehicle (ip) 3) Chronic mefenamic acid+hesperidin (ip) or DMSO (ip). CSD susceptibility was evaluated and behavioral testing was performed. SULT1A1 enzyme activity was measured in brain samples. Results Single-dose of hesperidin neither changed CSD susceptibility nor resulted in any behavioral change. Chronic mefenamic acid exposure resulted in increased CSD susceptibility, mechanical-thermal hypersensitivity, increased head shake, grooming and freezing and decreased locomotion. Single dose hesperidin administration after chronic mefenamic acid exposure resulted in increased CSD susceptibility and mechanical-thermal hypersensitivity, increased freezing and decreased locomotion. SULT1A1 enzyme activity was lower in mefenamic acid and mefenamic acid+hesperidin groups compared to their vehicles. Conclusion Mefenamic acid and hesperidin have synergistic effect in modulating CSD susceptibility and pain behavior. Sulfotransferase inhibition may be the common mechanism by which food triggers and NSAIDs modulate migraine susceptibility. Further investigations regarding human provocation studies using hesperidin in migraine patients with medication overuse are needed.

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“…All drug and vehicle injections were performed intraperitoneally. The administration doses of the drugs were chosen according to the literature as follows: nitroglycerin (NTG) 10 mg/kg (Kilinc et al, 2022a), apomorphine (Apm) 0.5 mg/kg (Greco et al, 2008), metoclopramide (Met) 1 mg/kg (Doganay Aydin et al, 2017), haloperidol (Hal) 1 mg/kg (Collins et al, 2014) and ondansetron (Ond) 0.5 mg/kg (Giorno et al, 2018). The migraine model was induced by a single administration of nitroglycerin.…”

Section: Experimental Groups and The Establishment Of In Vivo Migrain...mentioning

confidence: 99%

The effects and D2 receptor-mediated mechanisms of dopaminergic system modulation in in-vivo and in-vitro experimental models of migraine

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Torun

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2023

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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 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 brainstem were determined by ELISA. 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, while the other administrations were ineffective. Apomorphine-mediated dopaminergic activation exacerbated nitroglycerin-stimulated migraine pain by further enchancing 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 migrane like conditions.

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Metoclopramide inhibits trigeminovascular activation:evidence for effective acute attack treatment in migraine

Cited by 16 publications

References 15 publications

Aura and Head pain: relationship and gaps in the translational models

Aura and Head pain: relationship and gaps in the translational models

Migraine susceptibility is modulated by food triggers and analgesic overuse via sulfotransferase inhibition

The effects and D2 receptor-mediated mechanisms of dopaminergic system modulation in in-vivo and in-vitro experimental models of migraine

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