Effect of Adrenomedullin on Migraine-like Attacks in Patients With Migraine: A Randomized Crossover Study

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011930
Author(s):  
Hashmat Ghanizada ◽  
Mohammad Al-Mahdi Al-Karagholi ◽  
Nanna Arngrim ◽  
Mette Mørch-Rasmussen ◽  
Christopher S. Walker ◽  
...  
Keyword(s):  
Intravenous Infusion ◽  
Migraine Without Aura ◽  
Secondary Outcome ◽  
Heat Sensation ◽  
Headache Intensity ◽  
Potent Vasodilator ◽  
Migraine Pathogenesis ◽  
Double Blinded ◽  
Randomized Crossover Study ◽  
Placebo Infusion

ObjectiveTo determine whether the intravenous infusion of adrenomedullin, a potent vasodilator belonging to calcitonin family of peptides, provokes attacks of migraine in patients.MethodsTwenty migraine without aura patients participated in a placebo-controlled and double-blinded clinical study. In a randomized and crossover design the patients received an intravenous infusion of human adrenomedullin (19.9 picomole/kg/min) or placebo (saline) administrated via an automated intravenous pump (20 minutes). The patients participated in two study days with washout period of minimum of seven days. The primary outcome of the study was predefined as a difference in migraine incidence (0–12 h) and the secondary outcome were the headache intensity score’s area under curve (AUC0-12 h) and the (AUC 0-90 min) for MAP, flushing and HR.ResultsEleven migraine without aura patients (55%) fulfilled migraine attacks criteria after adrenomedullin infusion in comparison to only three patients reported attack (15%) after placebo (P= 0.039). We found that patients reported in a period of (0-12 hours) stronger headache intensity after adrenomedullin in comparison to placebo infusion (P= 0.035). AUC0-90 min for HR and, flushing (P < 0.05) were significant and MAP (P = 0.502) remain unchanged. Common adverse events reported were facial flushing, heat sensation and palpitation (P <0.001)ConclusionOur data implicate adrenomedullin in migraine pathogenesis. This suggests that adrenomedullin and/or its receptors are novel therapeutic targets for the treatment of migraine. However, we cannot discount for the possibility that adrenomedullin may be acting through the canonical CGRP receptor.

PACAP27 induces migraine-like attacks in migraine patients

Cephalalgia ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 57-67 ◽  
Author(s):  
Hashmat Ghanizada ◽  
Mohammad Al-Mahdi Al-Karagholi ◽  
Nanna Arngrim ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Adenylate Cyclase ◽  
Crossover Study ◽  
Migraine Without Aura ◽  
Pituitary Adenylate Cyclase ◽  
Associated Symptoms ◽  
Migraine Pathogenesis ◽  
Protein Isoform ◽  
To Receive ◽  
Placebo Infusion

Introduction Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the effect of human PACAP27 infusion on induction of migraine in a provocation model. Methods In a crossover study, 20 migraine without aura patients were randomly assigned to receive human PACAP27 (10 picomol/kg/min) or saline (placebo) infusion over 20 min. We recorded the migraine and associated symptoms. Results All patients completed the study. PACAP27 provoked migraine-like attacks in 11 patients (55%) and two developed attacks after placebo (10%) ( p = 0.022). The headache intensity and duration after PACAP27 was significantly greater compared to placebo ( p = 0.003). Conclusion PACAP27 triggers migraine attacks without aura. These novel data strengthen the role of PACAP and its receptors in migraine pathogenesis.

Two-hour infusion of vasoactive intestinal polypeptide induces delayed headache and extracranial vasodilation in healthy volunteers

Cephalalgia ◽  
2020 ◽  
Vol 40 (11) ◽  
pp. 1212-1223 ◽  
Author(s):  
Lanfranco Pellesi ◽  
Mohammad Al-Mahdi Al-Karagholi ◽  
Basit Ali Chaudhry ◽  
Cristina Lopez Lopez ◽  
Josefin Snellman ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Infusion ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Continuous Intravenous Infusion ◽  
Headache Intensity ◽  
Parasympathetic System ◽  
The Difference ◽  
Cranial Arteries

Background In recent years, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptides (PACAPs) have gained special interest in headache science. VIP and PACAPs (two isoforms, PACAP27 and PACAP38) are related in structure and function, as are their receptors, but they show differences in vasodilating- and headache-inducing properties. Intravenous infusion of PACAP27 or PACAP38, but not VIP, induces a long-lasting dilation of cranial arteries and delayed headache. The relationship between the long-lasting cranial vasodilation and headache development is not fully clarified. Methods In a double-blinded, placebo-controlled, crossover study in 12 healthy volunteers, diameter changes of cranial arteries, occurrence of headache and the parasympathetic system were examined before, during and after a 2-hour continuous intravenous infusion of VIP and placebo. Primary endpoints were the differences in area under the curve for the superficial temporal artery diameter and headache intensity scores, as well as in headache incidence, between VIP and placebo. Results The superficial temporal artery diameter was significantly larger on the VIP day compared to placebo ( p < 0.001) and the dilation lasted for more than 2 h. The incidence of headache was higher ( p = 0.003) on the VIP day compared to the placebo day. The difference in headache intensity scores was more evident in the post-infusion period (120–200 min, p = 0.034) and in the post-hospital phase (4–12 h, p = 0.025). Cranial parasympathetic activity, measured through the production of tears, was higher during VIP compared to placebo ( p = 0.033). Conclusion Continuous intravenous infusion of VIP over 2 h induced a long-lasting cranial vasodilation, activation of the cranial parasympathetic system, and delayed mild headaches in healthy volunteers. Trial Registration: The study is registered at ClinicalTrials.gov (NCT03989817).

scholarly journals Evaluation of mint efficacy regarding dysmenorrhea in comparison with mefenamic acid: A double blinded randomized crossover study

2016 ◽  
Vol 21 (4) ◽  
pp. 363 ◽  
Author(s):  
HoriehRezvani Asl ◽  
SeyedehZahra Masoumi ◽  
Jalal Poorolajal ◽  
MohammadHosseini Panah ◽  
SeyedehReyhaneh Oliaei
Keyword(s):  
Crossover Study ◽  
Mefenamic Acid ◽  
Double Blinded ◽  
Randomized Crossover Study

scholarly journals Intravenous versus Intra-Articular Tranexamic Acid in Primary Total Hip Arthroplasty: A Prospective Randomised Double Blinded Non-Inferiority Trial

2021 ◽  
Vol 11 ◽  
Author(s):  
Afsana Hasan ◽  
David Campbell ◽  
Peter Lewis
Keyword(s):  
Total Hip Arthroplasty ◽  
Blood Loss ◽  
Tranexamic Acid ◽  
Hip Arthroplasty ◽  
Mode Of Delivery ◽  
Secondary Outcome ◽  
Total Hip ◽  
Significant Difference ◽  
Double Blinded ◽  
Primary Total Hip Arthroplasty

Introduction Tranexamic acid (TXA) has been shown to be effective in reducing post-operative blood loss after hip replacement surgery. Clinicians can be reluctant to administer intravenous (IV) TXA to high risk patients and intra-articular (IA) administration has been proposed as an alternative mode of delivery. This study was conducted to compare the efficacy of IV versus IA administration of TXA.   Methods This prospective, double blinded, randomised non-inferiority trial, compared 69 patients undergoing primary total hip arthroplasty (THA) who received either 3 doses of 15mg/kg of IV TXA or 3 g of IA TXA after capsular closure. The primary outcomes were change in Hb and the rate of blood transfusion. The secondary outcome was the rate of VTE.   Results The mean haemoglobin level change from pre-operative to day 1 post-operative for the IV group was 26.7g/L and for IA group was 27.3g/L. No statistically significant difference was detected between the two groups (p=0.82). No patients required a transfusion or developed a VTE.   Conclusions IA administration of TXA can be equally effective as IV in the reduction of blood loss and the prevention of post-operative anaemia in primary THA.

scholarly journals Comparison of efficacy of needling and a combination of needling and platelet rich plasma in relieving pain and improving function in patients of tennis elbow: a prospective, randomized, double blinded, placebo controlled clinical trial

2021 ◽  
Vol 7 (2) ◽  
pp. 258
Author(s):  
Vikram Sharma ◽  
Vivek Chandak
Keyword(s):  
Tennis Elbow ◽  
Platelet Rich Plasma ◽  
Controlled Trial ◽  
Lateral Epicondylitis ◽  
Secondary Outcome ◽  
Controlled Clinical Trial ◽  
Group A ◽  
Group B ◽  
Double Blinded

<p><strong>Background: </strong>Lateral epicondylitis is a common musculoskeletal disorder for which an effective treatment strategy remains unknown. Aim of the study was to examine whether a single injection of platelet-rich plasma (PRP) with needling is more effective than needling with placebo in reducing pain in adults with lateral epicondylitis. Study design used was randomized controlled trial.    </p><p><strong>Methods: </strong>A total of 66 patients with chronic lateral epicondylitis were randomized (1:1) to receive either a blinded injection of PRP (group A) or saline (placebo) group B. The primary end point was a change in pain using the VAS and patient-rated tennis elbow evaluation (PRTEE) questionnaire. The secondary outcome being improvement in function (PRTEE scores).<strong></strong></p><p><strong>Results: </strong>The VAS score and PRTEE score improved significantly in both the groups at all 3 follow-up examinations. Group A had significantly better results than the group B.</p><p><strong>Conclusions: </strong>PRP injection are safe and effective management strategy for lateral epicondylitis</p>

Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients

Cephalalgia ◽  
2020 ◽  
Vol 40 (8) ◽  
pp. 842-850
Author(s):  
Katrine Falkenberg ◽  
Helene Rønde Bjerg ◽  
Jes Olesen
Keyword(s):  
Migraine Without Aura ◽  
Trial Registration ◽  
Double Blind ◽  
Drug Candidates ◽  
Headache Intensity ◽  
Subcutaneous Sumatriptan ◽  
The Difference ◽  
Novel Drug

Objectives The authors have previously tried to develop a model for the testing of novel drug candidates for migraine, using the headache and migraine provoking agent cilostazol. Previous studies have used sumatriptan tablets as the validating drug, but they were not sufficiently effective. In this study we test the effect of subcutaneous sumatriptan on cilostazol induced headache in patients with migraine without aura. Method Thirty patients with migraine without aura received 200 mg cilostazol on two different study days. The induced headache was treated with subcutaneous sumatriptan in a randomized, double-blind cross-over design. The patients filled out a self-reported headache questionnaire until 12 h after cilostazol. Results All 30 patients experienced headache (range 3–10) on both study days and the headache fulfilled the criteria for a migraine-like attack in 73% on the sumatriptan day and in 77% on the placebo day. Sumatriptan injection reduced the headache score 2 h after treatment ( p = 0.003). The difference between headache intensity on the sumatriptan day and the placebo day was significant at both 2 h ( p = 0.01) and 4 h ( p = 0.0007) after treatment. Conclusion Subcutaneous sumatriptan reduces cilostazol induced headache in migraine patients. The cilostazol model may be useful as a tool to test the potential of new anti-migraine drugs. Trial registration: The study is registered on clinicaltrials.gov (NCT03422796).

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial

Cephalalgia ◽  
2021 ◽  
pp. 033310242097539
Author(s):  
Nita Katarina Frifelt Wienholtz ◽  
Casper Emil Christensen ◽  
Ditte Georgina Zhang ◽  
Hande Coskun ◽  
Hashmat Ghanizada ◽  
...  
Keyword(s):  
Early Treatment ◽  
Intravenous Infusion ◽  
Migraine Without Aura ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Randomised Clinical Trial ◽  
Trigeminovascular System ◽  
Double Blind ◽  
Nociceptive Transmission

Objective To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. Results Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo ( p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) ( p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo ( p < 0.001). Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system. Trial Registration: ClinicalTrials.gov (NCT03881644).

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