Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine

Cernuda-Morollón, Eva; Martínez–Camblor, Pablo; Alvarez, Rocío; Larrosa, Davinia; Ramón, César; Pascual, Julio

doi:10.1177/0333102414535111

Cited by 75 publications

(83 citation statements)

References 27 publications

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“…Results from animal studies have provided evidence for an antinociceptive effect of onabotA mediated by repressing the local stimulated release of a number of inflammatory mediators from sensory neurons, again including CGRP. 12,18,25,37 When taken together, these experimental findings and our current results suggest that the primary mechanism of action of onabotA in CM is the reversal of peripheral and central sensitization as a result of the inhibition of the release of CGRP 2,7,12,15 and to a lesser degree also of other pain-producing molecules, 11,28,40 by TVS neurons. This proposal also explains the absence of efficacy of onabotA in episodic migraine, 29 a condition where sensitization of central neurons has not occurred.…”

Section: Discussionsupporting

confidence: 72%

“…Although these findings in nonresponders could be explained by limitations of this study, such as the absence of a control group, the fact that most of these patients remained on oral preventives, the relatively low numbers of nonresponders in our series, or the intrinsic and subjective variability of migraine, our results might indicate that some patients with a "CM" phenotype could suffer from other headaches (eg, psychogenic, tension-type headache or other secondary headaches) in which CGRP does not seem to be involved. 3 Alternatively, as shown by measuring VIP or PACAP levels in this condition, 11,38 in some patients with migraine, pain could be secondary to a predominant activation of the parasympathetic arm of the TVS. 32,40,41 This could explain the fact that the efficacy of pure CGRP antagonists "gepants" seems to be lower than that seen for triptans, 28 which are known to inhibit both CGRP and VIP release by the TVS.…”

Section: Discussionmentioning

confidence: 99%

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OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine

Cernuda-Morollón

Ramón

Martínez–Camblor

et al. 2015

Pain

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161

129

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OnabotulinumtoxinA (onabotA) has shown efficacy in chronic migraine (CM). Its mechanism of action, however, remains obscure. We have analysed whether treatment with onabotA is able to induce changes in interictal plasma calcitonin gene-related peptide (CGRP) concentrations, which have been shown to be increased in patients with CM. Calcitonin gene-related peptide levels were determined in samples obtained from the right antecubital vein using ELISA, outside a migraine attack and having taken no symptomatic medication in the previous 24 hours, in 83 patients with CM (average age 44 years; 94% females) before and 1 month after treatment with 155 to 195 U of onabotA. CGRP levels after onabotA treatment (median, 51.89 pg/mL; range, 199.4-10.2) were significantly lower as compared with CGRP levels obtained before onabotA treatment (median, 74.09 pg/mL; range, 241.0-11.4; P = 0.001). Pretreatment CGRP levels in responders (76.85 pg/mL) were significantly higher than those seen in nonresponders (50.45 pg/mL; P = 0.001). One month after treatment, the CGRP levels did not change in nonresponders (51.89 pg/mL; P not significant), but significantly decreased in responders (52.48 pg/mL; P = 0.003). A number of demographic factors, clinical features, and comorbidities were not different in responders as compared with those of nonresponders. These results confirm that interictal CGRP levels can be of help in predicting the response to onabotA and suggest that the mechanism of action of onabotA in CM is the reversal of sensitization as a result of the inhibition of CGRP release.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine

Cernuda-Morollón

Ramón

Martínez–Camblor

et al. 2015

Pain

Self Cite

161

129

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“…Intravenous infusion of VIP indeed caused vasodilation in the temporal superficial artery; however, it did not induce migraine attacks [97]. Interestingly though, a recent study has reported increased VIP levels in the serum of chronic migraine patients compared to healthy subjects [98]. In conclusion, we assume that VIP might have a strong vasodilator effect, but its role in initiating migraine attack is uncertain.…”

Section: Vasoactive Intestinal Peptidementioning

confidence: 64%

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Lukács

Tajti

Fülöp

et al. 2017

CMC

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Abstract:Background: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms. Objective: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation. Method: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published in January 2017. Results: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant result compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC 1 ), and kynurenic acid (KYNA) analogues. Conclusion: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

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“…Cernuda-Morollón et al [183], for example, measured serum VIP levels in patients with chronic and episodic migraine. Their research showed consistent, significant elevations in serum VIP among test subjects that suffered with migraines.…”

Section: How Do Pharmacological Interventions Take Advantage Of Pamentioning

confidence: 99%

Transmission pathways and mediators as the basis for clinical pharmacology of pain

Kirkpatrick

McEntire

Smith

et al. 2016

Expert Review of Clinical Pharmacology

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Introduction Mediators in pain transmission are the targets of a multitude of different analgesic pharmaceuticals. This review explores the most significant mediators of pain transmission as well as the pharmaceuticals that act on them. Areas Covered The review explores many of the key mediators of pain transmission. In doing so, this review uncovers important areas for further research. It also highlights agents with potential for producing novel analgesics, probes important interactions between pain transmission pathways that could contribute to synergistic analgesia, and emphasizes transmission factors that participate in transforming acute injury into chronic pain. Expert Commentary This review examines current pain research, particularly in the context of identifying novel analgesics, highlighting interactions between analgesic transmission pathways, and discussing factors that may contribute to the development of chronic pain after an acute injury.

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Increased VIP levels in peripheral blood outside migraine attacks as a potential biomarker of cranial parasympathetic activation in chronic migraine

Abstract: Increased interictal VIP level measured in peripheral blood could be a biomarker helping in CM diagnosis, though it does not clearly differentiate between EM and CM.

Cited by 75 publications

References 27 publications

OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine

OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Transmission pathways and mediators as the basis for clinical pharmacology of pain

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