Identifying New Antimigraine Targets: Lessons from Molecular Biology

Edvinsson, Lars; Haanes, Kristian Agmund

doi:10.1016/j.tips.2021.01.002

Cited by 16 publications

(14 citation statements)

References 93 publications

(107 reference statements)

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“…The data imply that this inflammatory signaling occurs in the trigeminocervical ganglia and the meninges. This signaling may be involved in the central nociceptive pathways of headache chronification ( 91 , 92 ). When meningeal nociceptive fibers are activated for a long time, they can release a variety of vasoactive peptides such as CGRP, pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, and neurokinin-A ( 73 , 93 ).…”

Section: Methodsmentioning

confidence: 99%

Immunologic aspects of migraine: A review of literature

et al. 2022

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Migraine headaches are highly prevalent, affecting 15% of the population. However, despite many studies to determine this disease's mechanism and efficient management, its pathophysiology has not been fully elucidated. There are suggested hypotheses about the possible mediating role of mast cells, immunoglobulin E, histamine, and cytokines in this disease. A higher incidence of this disease in allergic and asthma patients, reported by several studies, indicates the possible role of brain mast cells located around the brain vessels in this disease. The mast cells are more specifically within the dura and can affect the trigeminal nerve and cervical or sphenopalatine ganglion, triggering the secretion of substances that cause migraine. Neuropeptides such as calcitonin gene-related peptide (CGRP), neurokinin-A, neurotensin (NT), pituitary adenylate-cyclase-activating peptide (PACAP), and substance P (SP) trigger mast cells, and in response, they secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) as a selective result of corticotropin-releasing hormone (CRH) secretion. This stress hormone contributes to migraine or intensifies it. Blocking these pathways using immunologic agents such as CGRP antibody, anti-CGRP receptor antibody, and interleukin-1 beta (IL-1β)/interleukin 1 receptor type 1 (IL-1R1) axis-related agents may be promising as potential prophylactic migraine treatments. This review is going to summarize the immunological aspects of migraine.

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Section: Methodsmentioning

confidence: 99%

Immunologic aspects of migraine: A review of literature

et al. 2022

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“…Although the mechanisms underlying migraine remain poorly understood, several main potential mechanisms have been suggested by researchers, including the activation of meningeal afferents, neuropeptide release, abnormal cranial vasodilation, neurogenic inflammation, and central pain sensitization ( Edvinsson and Haanes, 2021 ). Much evidence supports that nitric oxide (NO) plays an important role in triggering migraine ( Thomsen and Olesen, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors via the Inhibition of Inflammation Mediated by Nitric Oxide Synthase

et al. 2022

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Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine via nitroglycerin (NTG) injection. The in vivo experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1β, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). In vitro, XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.

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“…An Anti-PACAP antibody is under development. The findings from this trial will give further clarifications about the role of PACAP in migraine pathophysiology [ 137 ].…”

Section: Neuropeptidesmentioning

confidence: 99%

New Insights on Metabolic and Genetic Basis of Migraine: Novel Impact on Management and Therapeutical Approach

Simonetta

Riolo

Todaro

et al. 2022

IJMS

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Migraine is a hereditary disease, usually one-sided, sometimes bilateral. It is characterized by moderate to severe pain, which worsens with physical activity and may be associated with nausea and vomiting, may be accompanied by photophobia and phonophobia. The disorder can occur at any time of the day and can last from 4 to 72 h, with and without aura. The pathogenic mechanism is unclear, but extensive preclinical and clinical studies are ongoing. According to electrophysiology and imaging studies, many brain areas are involved, such as cerebral cortex, thalamus, hypothalamus, and brainstem. The activation of the trigeminovascular system has a key role in the headache phase. There also appears to be a genetic basis behind the development of migraine. Numerous alterations have been identified, and in addition to the genetic cause, there is also a close association with the surrounding environment, as if on the one hand, the genetic alterations may be responsible for the onset of migraine, on the other, the environmental factors seem to be more strongly associated with exacerbations. This review is an analysis of neurophysiological mechanisms, neuropeptide activity, and genetic alterations that play a fundamental role in choosing the best therapeutic strategy. To date, the goal is to create a therapy that is as personalized as possible, and for this reason, steps forward have been made in the pharmacological field in order to identify new therapeutic strategies for both acute treatment and prophylaxis.

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Identifying New Antimigraine Targets: Lessons from Molecular Biology

Abstract: Neuroimaging experiments propose that the migraine attack originates in the hypothalamus. A further mismatch in the communication or tuning of the trigeminovascular system, might lead to calcitonin gene-related peptide (CGRP) release, sensitization, and migraine pain.

Cited by 16 publications

References 93 publications

Immunologic aspects of migraine: A review of literature

Immunologic aspects of migraine: A review of literature

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors via the Inhibition of Inflammation Mediated by Nitric Oxide Synthase

New Insights on Metabolic and Genetic Basis of Migraine: Novel Impact on Management and Therapeutical Approach

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