Reliability of the Nitroglycerin Provocative Test in the Diagnosis of Neurovascular Headaches

Sances, Grazia; Tassorelli, Cristina; Pucci, Ennio; Ghiotto, Natascia; Sandrini, Giorgio; Nappi, Giuseppe

doi:10.1111/j.1468-2982.2004.00639.x

Cited by 126 publications

(135 citation statements)

References 35 publications

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“…These proportions were based on small numbers, but subsequent studies have demonstrated almost identical figures in large numbers of patients. 36,37 The migraine aura is probably caused by a so-called cortical spreading depression, 38 which is a slowly spreading depolarization of all cellular elements of the cerebral cortex; this phenomenon is associated with the production of NO. Indeed, the GTN experiments previously described herein suggest that the aura may produce headache via the production of NO.…”

Section: Migrainementioning

confidence: 99%

Nitric Oxide-Related Drug Targets in Headache

Olesen

2010

Neurotherapeutics

103

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Summary: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache. Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine.Similar evidence suggests an important role of NO in the tension-type headache and cluster headache.These very strong data from human experimentation make it highly likely that antagonizing NO effects will be effective in the treatment of primary headaches. Nonselective NOS inhibitors are likely to have side effects whereas selective compounds are now in early clinical trials. Antagonizing the rate limiting cofactor tetrahydrobiopterin seems another very likely new treatment. It is more unlikely that antagonism of cGMP or its formation will be feasible, but augmenting its breakdown via phosphodiesterase activation is a possibility, as well as other ways of inhibiting the NO-cGMP pathway.

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Section: Migrainementioning

confidence: 99%

Nitric Oxide-Related Drug Targets in Headache

Olesen

2010

Neurotherapeutics

103

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“…Among the mediators of migraine-associated hyperalgesia, nitric oxide (NO) has been implicated in the periphery as well as at central sites. The systemic administration of nitroglycerin (NTG), an NO donor, provokes spontaneous migrainelike attacks (2), and the facilitation of pain transmission at the spinal level only in migraine patients (3), probably as a consequence of a sensitization phenomenon (4). Analogously, in the rat, NTG induces a condition of hyperalgesia detectable as an increase in the nocifensive response to the plantar and orofacial formalin tests (5,6).…”

Section: Introductionmentioning

confidence: 99%

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

et al. 2016

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Background: Trigeminal sensitization represents a major mechanism underlying migraine attacks and their recurrence. Nitroglycerin (NTG) administration provokes spontaneous migraine-like headaches and in rat, an increased sensitivity to the formalin test. Kynurenic acid (KYNA), an endogenous regulator of glutamate activity and its analogues attenuate NTG-induced neuronal activation in the nucleus trigeminalis caudalis (NTC). The anti-hyperalgesic effect of KYNA analogue 1 (KYNA-A1) was investigated on animal models specific for migraine pain. Aim: Rats made hyperalgesic by NTG administration underwent the plantar or orofacial formalin tests. The effect of KYNA-A1 was evaluated in terms of nocifensive behavior and of neuronal nitric oxide synthase (nNOS), calcitonin generelated peptide (CGRP) and cytokines expression in areas involved in trigeminal nociception. Results: KYNA-A1 abolished NTG-induced hyperalgesia in both pain models; NTG alone or associated to formalin injection induced an increased mRNA expression of CGRP, nNOS and cytokines in the trigeminal ganglia and central areas, which was reduced by KYNA-A1. Additionally, NTG caused a significant increase in nNOS immunoreactivity in the NTC, which was prevented by KYNA-A1. Conclusion: Glutamate activity is likely involved in mediating hyperalgesia in an animal model specific for migraine. Its inhibition by means of a KYNA analogue modulates nNOS, CGRP and cytokines expression at peripheral and central levels.

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“…Nitroglycerin (NTG) is a vasodilator known to induce spontaneous-like headache attacks in migraine sufferers (3), probably as a consequence of sensitization phenomena (4). Indeed, NTG administration to migraineurs is related to lower temporal summation threshold and increased painful sensation, when compared to baseline, to placebo condition and to controls.…”

Section: Introductionmentioning

confidence: 99%

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

et al. 2015

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Background Systemic nitroglycerin (NTG) activates brain nuclei involved in nociceptive transmission as well as in neuroendocrine and autonomic functions in rats. These changes are considered relevant for migraine because NTG consistently provokes spontaneous-like migraine attacks in migraineurs. Several studies have suggested a relationship between the endocannabinoid levels and pain mediation in migraine. URB937, a peripheral inhibitor of fatty acid amide hydrolase (FAAH)—the enzyme that degrades anandamide, produces analgesia in animal models of pain, but there is no information on its effects in migraine. Aim We evaluated whether URB937 alters nociceptive responses in the animal model of migraine based on NTG administration in male rats, using the tail flick test and the plantar and orofacial formalin tests, under baseline conditions and after NTG administration. Furthermore, we investigated whether URB937 affects NTG-induced c-Fos expression in the brain. Results During the tail flick test, URB937 showed an antinociceptive effect in baseline conditions and it blocked NTG-induced hyperalgesia. URB937 also proved effective in counteracting NTG-induced hyperalgesia during both the plantar and orofacial formalin tests. Mapping of brain nuclei activated by NTG indicates that URB937 significantly reduces c-Fos expression in the nucleus trigeminalis caudalis and the locus coeruleus. Conclusions The data suggest that URB937 is capable of changing, probably via indirect mechanisms, the functional status of central structures that are important for pain transmission in an animal model of migraine.

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Reliability of the Nitroglycerin Provocative Test in the Diagnosis of Neurovascular Headaches

Cited by 126 publications

References 35 publications

Nitric Oxide-Related Drug Targets in Headache

Nitric Oxide-Related Drug Targets in Headache

Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms

Effects of peripheral FAAH blockade on NTG-induced hyperalgesia—evaluation of URB937 in an animal model of migraine

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