Nitroglycerin as a model of migraine: Clinical and preclinical review

Sureda-Gibert, Paula; Akerman, Simon

doi:10.1016/j.ynpai.2022.100105

Cited by 28 publications

(22 citation statements)

References 180 publications

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“…Nitroglycerin (NG) as a NO donor is widely used both to model an episodic migraine with a single injection and chronic migraine with multiple injections [40][41][42][43][44]. Chronic administration of NG in our study caused the development of allodynia and photophobia, which confirms the development of symptoms of migraine in rats.…”

Section: Discussionsupporting

confidence: 79%

“…Chronic administration of NG in our study caused the development of allodynia and photophobia, which confirms the development of symptoms of migraine in rats. A single injection of NG to rodents (10 mg/kg) causes the sensitization of both primary afferent (trigeminal ganglion) and central trigeminocervical neurons [43,45,46]. Such types of sensitization may be caused by the release of pro-inflammatory agents participated in the pathogenesis of migraine such as PACAP, BDNF [47], and CGRP [48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

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Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve

Koroleva

Svitko

Ananev

et al. 2023

IJMS

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Nitric oxide is one of the endogenous molecules that play a key role in migraine. However, the interaction between NO and the main players in the nociceptive activity of the meningeal trigeminal afferents—TRPV1 and P2X3 receptors—remains unstudied. In the current project, the effects of acute and chronic NO administration on the activity of TRPV1 and P2X3 receptors in the peripheral afferents were studied using electrophysiological recording of action potentials of the trigeminal nerve in the rat hemiskull preparations. The data obtained indicate that exogenous and endogenous NO increased the activity of the trigeminal nerve independent on the inhibition of the TRPV1 and P2X3 receptors. The activity of the trigeminal nerve triggered by ATP changed neither in acute incubation in the NO donor—sodium nitroprusside (SNP) nor in the chronic nitroglycerine (NG)-induced migraine model. Moreover, the chronic NG administration did not increase in the number of degranulated mast cells in the rat meninges. At the same time, the capsaicin-induced activity of the trigeminal nerve was higher with chronic NO administration or after acute NO application, and these effects were prevented by N-ethylmaleimide. In conclusion, we suggested that NO positively modulates the activity of TRPV1 receptors by S-nitrosylation, which may contribute to the pro-nociceptive action of NO and underlie the sensitization of meningeal afferents in chronic migraine.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve

Koroleva

Svitko

Ananev

et al. 2023

IJMS

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“…On the other hand, we tested the behavioural responses in the hind paw following the NTG injection. It is well‐established that behavioural responses in the hindpaws following NTG administration in both acute and chronic migraine models are indicative of migraine‐like extracephalic allodynia in patients (Burstein et al, 2010; Sureda‐Gibert et al, 2022; Vuralli et al, 2019). However, if we also tested behavioural responses in the orofacial or periorbital region in addition to the hind‐paw, it would further strengthen our findings because migraine‐related pain mostly originates from the trigeminal nerve (Messlinger, 2009; Olesen et al, 2009), which carries sensory information from the head and face.…”

Section: Discussionmentioning

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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“…In addition, other symptoms such as unilateral headache, prodromal symptoms such as yawning, tiredness, neck stiffness ( Maniyar et al, 2014 ), as well as cranial allodynia ( Akerman et al, 2019 ) have been experienced by study participants exposed to nitroglycerin. As there is a high response rate to nitroglycerin administration, another strength of this model is its reproducibility ( Sureda-Gibert et al, 2022 ). There are no reports of nausea or vomiting associated with the nitroglycerin model, although phonophobia and photophobia have been documented in clinical studies ( Karsan et al, 2021 ).…”

Section: Human Experimental Migraine Modelmentioning

confidence: 99%

Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics

Frimpong-Manson,

Ortiz,

McMahon

et al. 2024

Front. Mol. Neurosci.

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The individual and global burden of migraine is of such significance that there are accelerated efforts to develop new therapies. New migraine therapeutics are needed to address the current deficiencies that exist in the efficacy and adherence rate of approved anti-migraine medications. The recent discovery of the calcitonin gene related peptide as an add-on to the role of serotonin has markedly increased the range of new treatment options for acute and chronic migraine. Despite this, tackling the complexity of migraine disorders requires a complete understanding of its pathophysiology. Preclinical animal models can shed light on disease-related pathophysiology, including migraine. Indeed, the use of animal models has been instrumental in developing many therapeutics. However, an animal model is limited by the predictive and face validity of that model, and this extends to preclinical migraine models. In this review, a summary of the current understanding of the pathophysiology of migraine is given from both a preclinical and clinical perspective, and an emphasis is placed on the animal models of migraine. We will discuss the strengths and pitfalls of common preclinical migraine models as well as experimental research areas to explore further.

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Nitroglycerin as a model of migraine: Clinical and preclinical review

Cited by 28 publications

References 180 publications

Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve

Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve

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

Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics

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