Calcitonin gene-related peptide receptor antagonists for migraine

Fischer, Michael J.M.

doi:10.1517/13543784.2010.490829

Cited by 22 publications

(16 citation statements)

References 96 publications

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“…In the dorsal horn, CGRP can enhance glutamate transmission by presynaptic mechanisms, leading to central sensitization (117, 118). In the trigeminal nucleus, CGRP release from central terminals of the trigeminal nerve can modulate second-order nociceptive neurons in the TNC (119). Expression studies revealed that the TNC CGRP receptors are present on presynaptic afferent terminals but not on postsynaptic second-order neurons (90).…”

Section: How Does Cgrp Contribute To Migraine?mentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

308

299

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Migraine is a neurological disorder that manifests as a debilitating headache associated with altered sensory perception. The neuropeptide calcitonin gene-related peptide (CGRP) is now firmly established as a key player in migraine. Clinical trials carried out during the past decade have proved that CGRP receptor antagonists are effective for treating migraine, and antibodies to the receptor and CGRP are currently under investigation. Despite this progress in the clinical arena, the mechanisms by which CGRP triggers migraine remain uncertain. This review discusses mechanisms whereby CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Future studies on epistatic and epigenetic regulators of CGRP actions are expected to shed further light on CGRP actions in migraine. In conclusion, targeting CGRP represents an approachable therapeutic strategy for migraine.

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Section: How Does Cgrp Contribute To Migraine?mentioning

confidence: 99%

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

308

299

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“…In the ascending pain pathway, remote from the site of cortical injury, CGRP is expressed and released from the peripheral terminals of the trigeminal ganglia, neuronal cell bodies, and central terminals in the brainstem. 47,72 CGRP in the trigeminal ganglia neurons and perivascular nerve fibers surrounding the meningeal and cerebral blood vessels acts as a potent vasodilator facilitating cerebral perfusion, but also plays an important role in nociceptive neurotransmission. Studies using sensitive tracers identified the trigeminal nerve and upper cervical ganglia as the afferent pain pathway for the meningeal and cerebral vessels, in which CGRP and NO are important signaling molecules.…”

Section: Trauma-induced Pain Signaling Molecules and Their Modulationmentioning

confidence: 99%

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

Daiutolo

Tyburski

Clark

et al. 2016

Journal of Neurotrauma

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The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle ( p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT ( p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia ( p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days ( p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH.

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“…Moreover, it is a neuromodulator that can enhance the glutamate transmission by presynaptic mechanisms in the dorsal horn [44] and in the trigeminal nucleus [45], resulting in central sensitization. CGRP could also play a role in the synaptic transmission to the amygdala and stria terminalis involved in fear responses [46], and in the synaptic transmissions between the lateral parabrachial nucleus and the amygdala central nucleus involved in pain-related behaviors [47].…”

Section: Cgrp As Mainstream In Migraine Pathophysiologymentioning

confidence: 99%

Chronic migraine treatment: from OnabotulinumtoxinA onwards

Negro

Curto

Lionetto

et al. 2016

Expert Review of Neurotherapeutics

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Our goal is to review the existing data on OnabotulinoumtoxinA and CGRP-targeting drugs such as anti-CGRP monoclonal antibodies, one of the most promising migraine drugs under development. The research of bibliographic databases has included only published peer-reviewed articles from indexed journals. Expert commentary: To date, real-life studies are supporting OnabotulinumtoxinA in the treatment of chronic migraine. Additionally, anti-CGRP mAbs showed good efficacy and safety in recent RCTs and may soon contribute to improve the quality of life of patients suffering with migraine.

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Calcitonin gene-related peptide receptor antagonists for migraine

Abstract: CGRP receptor antagonists will provide an additional and valuable therapeutic option for the treatment of headaches.

Cited by 22 publications

References 96 publications

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

Chronic migraine treatment: from OnabotulinumtoxinA onwards

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