PACAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor

Jansen‐Olesen, Inger; Baun, Michael; Amrutkar, Dipak Vasantrao; Ramachandran, Roshni; Christophersen, Daniel Vest; Olesen, Jes

doi:10.1016/j.npep.2014.01.004

Cited by 71 publications

(66 citation statements)

References 46 publications

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“…PACAP levels are elevated in migraine, and PACAP injection can induce migraine, similar to CGRP. PACAP also triggers CGRP release in the TNC (147), which further supports a cooperative action of these peptides. For a more complete comparison of CGRP and PACAP activities relevant to migraine, see Reference 112.…”

Section: Future Directions: Epistatic Partners and Epigenetic Regulatsupporting

confidence: 56%

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

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

300

296

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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: Future Directions: Epistatic Partners and Epigenetic Regulatsupporting

confidence: 56%

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

Russo

2015

Annu. Rev. Pharmacol. Toxicol.

300

296

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“…Our results draw attention to a possible influence between the PACAP and CGRP systems in migraine pathogenesis [125,220,221]. In addition there are evidence that PACAP shares expression and regulation simultaneous with CGRP [27,155,222].…”

Section: Possible Relations Between the Pacap-38 And Cgrp In Migraineurssupporting

confidence: 52%

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

Tuka¹

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“…Other possible mechanisms include sensitization of perivascular trigeminal afferents by vasoactive and neurogenic inflammatory pathways, mast cell degranulation, calcitonin gene-related peptide release from the trigeminal nucleus caudalis, and systemic effects. 3,9 Further comparison studies of PACAP38-induced migraine and spontaneous migraine are required to validate this model, which has exciting therapeutic implications in the form of pituitary adenylate cyclase-activating polypeptide type I receptor antagonists.…”

Section: Resultsmentioning

confidence: 99%

Journal Club: Change in brain network connectivity during PACAP38-induced migraine attacks

et al. 2016

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Journal Club: Change in brain network connectivity during PACAP38-induced migraine attacksThere is evidence to suggest that migraine attacks involve changes in complex neuronal networks that can be measured using functional MRI (fMRI) methods including resting state functional connectivity (RSFC). Networks that have previously been shown to be involved in the sensory and affective aspects of pain perception include the default mode network (DMN), salience network (SN), and sensorimotor network (SMN) (figure).1 In a recent study, Amin et al. 2 examined the RSFC of these 3 networks at baseline and in the early phases of experimentally induced migraine in patients with migraine without aura. In order to capture the early phases of migraine, corresponding to the time closest to migraine attack onset, migraine attacks were induced using the potent vasodilator neuropeptide pituitary adenylate cyclase-activating polypeptide-38 (PACAP38). 3 Since vasodilators can alter hemodynamics and potentially confound the fMRI signal, another vasodilator, vasoactive intestinal peptide (VIP), was used as a control since it also acts on extracranial arteries, but is much less likely (,20%) to provoke migraine-like attacks. 3HYPOTHESIS AND DESIGN Amin et al. hypothesized that patients would have altered RSFC of the DMN, SN, and SMN during the early phases of migraine compared to baseline. Abnormalities in the connectivity and activity of these resting-state networks have previously been reported during the interictal phase of migraine. 4,5 Patients were recruited as part of a larger study investigating the migraine-inducing properties of PACAP38 and VIP and their effects on extracranial and intracranial arterial diameter among other factors. 3A double-blind randomized design was used to allocate 24 patients to receive an IV infusion of either PACAP38 (10 pmol/kg/min) or VIP (8 pmol/kg/min) over 20 minutes on the first study day. On the second study day, which occurred at least 1 week after the first, patients received an infusion of the alternate vasodilator (i.e., the one they did not receive on the first day). Resting-state fMRI scans were acquired at baseline and at fixed timepoints thereafter.METHODS Eligible female participants meeting the inclusion criteria were included in the study if they had a verified diagnosis of migraine without aura according to the International Classification of Headache Disorders II. Resting-state fMRI scans were acquired at baseline and at 3 fixed time points after the start of infusion: 30, 130, and 310 minutes. An exception was if patients reported a migraine-like attack, in which case they were scanned immediately. Patients were migraine-free for 5 days and headache-free for 48 hours prior to baseline scans. To examine the early phase of PACAP38-induced migraine, the preattack time point that was closest to the attack onset was used in the RSFC analyses. The PACAP38 group consisted of 16 patients who all experienced migraine attacks after PACAP38 infusion, and the VIP group comprised 15 patie...

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PACAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor

Cited by 71 publications

References 46 publications

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

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

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

Journal Club: Change in brain network connectivity during PACAP38-induced migraine attacks

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