A prospective study of headache and neuropeptides in patients with pituitary adenomas

Cephalalgia ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 1049-1057
Author(s):  
Yixin Zhang ◽  
Qi Pan ◽  
Huahua Jiang ◽  
Gang Yang ◽  
Lixue Chen ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Calcitonin Gene Related Peptide ◽  
Clinical Criteria ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Post Operation ◽  
Stabbing Headache ◽  
A Prospective Study

Objective To evaluate clinical criteria for headache associated with pituitary adenoma (HaPA) in the International Classification of Headache Disorders (ICHD) 3rd edition version criteria and further determine whether elevations of plasma calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide 1-38 (PACAP1-38) concentration contribute to HaPA. Methods Demographic and clinical features of consecutive patients with pituitary adenoma were recorded. Plasma calcitonin gene-related peptide and PACAP1-38 concentrations in pituitary adenoma patients within 72 h pre- and post-operation were measured. Primary outcome for HaPA patients were 50% reduction of moderate-to-severe headache days at 3 months after discharge. Results Sixty-three patients with pituitary adenoma were recruited, 33 (52.4%) of whom had headache. The patients who had HaPA presented with migraine-like (32.9%), tension-type-like (12.1%), and stabbing headache (9.1%). Non-functional adenoma was present in the majority of cases (82.5%). Surgical resection improved headache in 83.3% of cases at 3 month follow-up. Pre- and post-operative calcitonin gene-related peptide and PACAP1-38 levels were significantly higher in patients with headache than in those without headache ( p < 0.05). Plasma calcitonin gene-related peptide and PACAP1-38 levels at 72 h post-operation were lower at 72 h after operation in patients who had greater improvement in headache compared with those who had little improvement, while plasma calcitonin gene-related peptide and PACAP1-38 levels were similar between these two groups preoperatively. Conclusions Most pituitary adenoma patients have non-functional adenoma, and half of this group have HaPA, indicating that the ICHD-3 criteria for HaPA with the emphasis on secretion status need further modifications. Lower plasma calcitonin gene-related peptide and PACAP1-38 concentrations at 72 h after operation may predict a better outcome in patients with HaPA.

Abstract P643: Incidence of Ischemic Stroke Among Migraineurs on Calcitonin Gene-Related Peptide Inhibitors

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Juliana Gomez ◽  
Mark Burish ◽  
Sean I Savitz ◽  
Louise D McCullough ◽  
Cecilia Ganduglia Cazaban
Keyword(s):  
Ischemic Stroke ◽  
Age Groups ◽  
Vascular Risk Factor ◽  
The United States ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Administrative Dataset ◽  
Calcitonin Gene

Introduction: Migraine is common and often disabling. Recent research has focused on a new class of treatments targeting the pain-signaling molecule calcitonin-gene-related peptide (CGRP). CGRP inhibitors are the first preventive therapies designed specifically for migraine. However, CGRP also induces vasodilation, and plays a role in cerebral blood flow autoregulation. The clinical cerebrovascular effects of long-term blockade of CGRP are not yet known. Methods: We analyzed a retrospective cohort of migraine patients from a large administrative dataset in the United States (OPTUM) that covers patients with commercial insurance and Medicare Advantage, during 2018 and 2019, using ICD-10 codes for all types of migraines. Migraine patients were divided into two groups based on their use of CGRP inhibitors (erenumab, fremanezumab, galcanezumab). We determined the incidence of stroke during 2018 and 2019 among both groups. For the group of migraine patients who used CGRP inhibitors, we focused on the incidence of stroke after these medications were initiated. Results: We identified 646,404 migraine patients; 18, 692 (2.9%) of them had used a CGRP inhibitor. Among the users of CGRP inhibitors, 86% were females, and 58% of patients were in the 41 to 65-year-old range. The average time of follow-up was 197 days after initiation of the medication. A total of 1.3 % of patients who used CGRP inhibitors had an ischemic stroke during the follow-up period versus 2.4% of patients who did not use CGRP inhibitors. The lower rate of stroke in the CGRP antibody group was found in both sexes and all age groups. Conclusions: These preliminary results suggest that CGRP inhibitors are not associated with a higher frequency of stroke in the initial months of use. This could be related to the avoidance of these medications in patients with known cardiovascular risk factors. Further analyses will be completed on vascular risk factor incidence in these populations as well as multiple regression. Prospective, long term studies are needed to confirm these results.

Neuropeptide Regulation of Interleukin-6 Production from the Pituitary: Stimulation by Pituitary Adenylate Cyclase Activating Polypeptide and Calcitonin Gene-Related Peptide*

Endocrinology ◽  
1991 ◽  
Vol 129 (4) ◽  
pp. 1797-1804 ◽  
Author(s):  
ICHIRO TATSUNO ◽  
ANIKO SOMOGYVARI-VIGH ◽  
KEIKO MIZUNO ◽  
PAUL E. GOTTSCHALL ◽  
HIROYOSHI HIDAKA ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Interleukin 6 ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase

Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system

Cephalalgia ◽  
2020 ◽  
Vol 40 (12) ◽  
pp. 1296-1309 ◽  
Author(s):  
Jacob Carl Alexander Edvinsson ◽  
Anne-Sofie Grell ◽  
Karin Warfvinge ◽  
Majid Sheykhzade ◽  
Lars Edvinsson ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Trigeminal Ganglion ◽  
Calcitonin Gene Related Peptide ◽  
Receptor Subtype ◽  
Primary Headaches ◽  
Satellite Glial Cells ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Peptide Release

Background Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.

scholarly journals Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue

2021 ◽  
Author(s):  
Simon Bentsen ◽  
Anette Sams ◽  
Philip Hasbak ◽  
Lars Edvinsson ◽  
Andreas Kjaer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Perfusion ◽  
Ct Scan ◽  
Calcitonin Gene Related Peptide ◽  
Coronary Perfusion ◽  
Inotropic Effects ◽  
Peptide Analogue ◽  
Related Peptide ◽  
Calcitonin Gene

Abstract Background Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction. Methods Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [99mTc]Tc-sestamibi SPECT/CT scan. Results Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats. Conclusion The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.

Les avancées dans les traitements de crise et de fond de la maladie migraineuse

2019 ◽  
Vol 213 (1-2) ◽  
pp. 59-64 ◽  
Author(s):  
Dominique Valade
Keyword(s):  
Ion Channels ◽  
Adenylate Cyclase ◽  
Phase I ◽  
Neuropeptide Y ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Acid Sensing Ion Channels ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Anticorps Monoclonaux

Le traitement de la crise migraineuse repose actuellement sur les anti-inflammatoires non stéroïdiens (AINS) et les triptans, qui sont les deux seules classes pharmacologiques dont l’efficacité thérapeutique a été démontrée avec un haut niveau de preuve dans cette indication. Ces deux classes pharmacologiques ne couvrent cependant pas tous les besoins thérapeutiques des migraineux. Deux programmes de développement clinique méritent une attention particulière et concernent les antagonistes des récepteurs du CGRP et les agonistes du récepteur 5-HT1F de la sérotonine. L’approche prophylactique est un élément capital du traitement de la migraine épisodique qui concerne plus d’un tiers des migraineux. Actuellement, cette approche prophylactique est possible au travers de plusieurs traitements pharmacologiques ayant un bon niveau de preuve dans cette indication et appartenant à diverses classes pharmacologiques : bêta-bloquants (propranolol, métoprolol), antiépileptiques (divalproate de sodium, topiramate, gabapentine), inhibiteurs calciques (flunarizine), antidépresseurs tricycliques et antagonistes sérotoninergiques (pizotifène). L’approche prophylactique peut également faire appel en seconde intention à des molécules mises plus récemment sur le marché mais dont le niveau de preuve dans cette indication est plus faible : vérapamil, venlafaxine, lisinopril et candesartan. Enfin, il convient de ne pas oublier l’utilisation d’anciens traitements (oxétorone) toujours en usage dans certains pays (comme la France). Devant le manque de spécificité, de nouveaux médicaments émergent, les plus importants étant les anticorps monoclonaux antagonistes du Calcitonin Gene-Related Peptide (CGRP), mais de nombreux autres sont en phase I ou II de recherche tels que les modulateurs de la fonction endothéliale, les antagonistes orexinergiques, l’ocytocine, les inhibiteurs non sélectifs des phosphodiestérases, les modulateurs des jonctions communicantes. Enfin, un futur plus lointain repose sur les neuropeptides hypothalamiques (Pituitary Adenylate Cyclase-Activating Polypeptide, PACAP ; neuropeptide Y, NPY), les inhibiteurs de synthèse de l’oxyde nitrique (NO) et les canaux ioniques activés par l’acidité extracellulaire (ASIC, Acid-Sensing Ion Channels).

scholarly journals Safety efficacy and tolerability of the calcitonin gene-related peptide monoclonal antibodies for migraine prevention in a real world setting

2021 ◽  
Author(s):  
Jasem Yousef Al-Hashel ◽  
Raed Alroughani ◽  
Hasan Kh Ashkanani ◽  
Ohood AlMutairi ◽  
Amr Akl ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Monoclonal Antibodies ◽  
Preventive Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
The Mean ◽  
Headache Pain

Abstract Background:Calcitonin gene-related peptide (CGRP) monoclonal antibodies were approved as preventive treatment for migraine. We aimed to assess CGRP monoclonal antibodies efficacy and safety.Methods:Patients were diagnosed based on International Classification of Headache Disorders disorders-third edition, (ICHD-III). Eligible patients received CGRP monoclonal antibodies (mAbs) and had a follow up visits for at least three months. Primary end point was a 50% or greater reduction in mean migraine days per month at the last visit. Secondary end points were change from baseline to last visit in the mean number of migraine days per month, change in the number of days of use of analgesics, change in the severity of headache pain, and change in scores on the Quality of life (QOL) questionnaire. Safety and tolerability were reported.Results:This prospective study included 63 migraine patients, with a mean age of 44.59 years. Females represented 77.8% of the cohort. A 50% or greater reduction in the mean number of migraine days per month was achieved in 68.3% of patients. At the last visit, patients had a significant reduction in migraine days, number of days of analgesic-usage and the severity of headache (5.13+ 4.11versus 14.04 + 7.77; p < 0.01), (6.43+ 6.34 versus 15.85 +7.31; p <. 0001), (5.40 +2.48 versus 9.67+ 0.72; p < 0.001) respectively. CGRP mAb treatment significantly improved quality of life (112.20+ 12.20 versus 92.13 +15.84; P< 0.001). 14.4% reported adverse events.Conclusion:Prophylactic CGRP monoclonal antibodies treatment for migraine were efficacious and reduced the number of monthly migraine days and the use of days of analgesics.

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