| 1. |
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| 2. |
- Andersson, JLR, et al.
(författare)
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Regional cerebral blood flow and oxygen metabolism during migraine with and without aura
- 1997
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Ingår i: CEPHALALGIA. - : SCANDINAVIAN UNIVERSITY PRESS. - 0333-1024. ; 17:5, s. 570-579
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO(2)) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6),
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| 3. |
- Ashina, Messoud, et al.
(författare)
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Real-world effectiveness of fremanezumab for the preventive treatment of migraine : Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study
- 2023
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Ingår i: Cephalalgia. - 0333-1024. ; 43:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. Methods: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1–12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1–12. Safety was assessed through adverse events reported. Results: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1–12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. Conclusion: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries. Trial registration: encepp.eu: EUPAS35111.
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| 4. |
- Baad-Hansen, L, et al.
(författare)
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Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity
- 2010
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Ingår i: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 30:1, s. 68-76
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.
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| 5. |
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| 6. |
- Becker, C., et al.
(författare)
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Migraine incidence, comorbidity and health resource utilization in the UK
- 2008
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:1, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- Population-based data on migraine incidence and comorbidity are scarce. We therefore aimed to quantify incidence rates and comorbidity of diagnosed migraine and health resource utilization (HRU) in migraineurs in the UK primary care setting. We conducted a follow-up study with a nested case-control analysis on the General Practice Research Database. The study encompassed 51 688 patients with a first-time diagnosis of migraine between 1994 and 2001, and the same number of matched controls. The migraine incidence rate was 3.69 (95± confidence interval 3.66, 3.73) cases per 1000 person-years. It was around 2.5 times higher in women. Most chronic diseases were slightly more prevalent in migraineurs than in controls. Triptan users had higher health resource utilization than other migraineurs. This study shows that migraine is a common diagnosis in general practice and associated with a high prevalence of comorbidity. The increased HRU in triptan users suggests greater migraine severity.
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| 7. |
- Belin, AC
(författare)
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Board Walk - January 2022
- 2022
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Ingår i: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 42:1, s. 87-
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 9. |
- Boles, RG, et al.
(författare)
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Sex ratios and mitochondrial genetics in migraine
- 2008
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Ingår i: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 28:9, s. 1001-1002
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
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| 11. |
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| 12. |
- Edvinsson, Jacob Carl Alexander, et al.
(författare)
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Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
- 2020
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Edvinsson, Lars
(författare)
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Blockade of CGRP receptors in the intracranial vasculature: a new target in the treatment of headache.
- 2004
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 24:8, s. 611-622
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Forskningsöversikt (refereegranskat)abstract
- In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with any of the other neuronal messengers. The purpose of this review is to describe the role of CGRP in the intracranial circulation and to elucidate a possible role for a specific CGRP receptor antagonist in the treatment of primary headaches. Acute treatment with a 5-HT1B/1D agonist (triptan) results in alleviation of the headache and normalization of the cranial venous CGRP levels, in part due to a presynaptic inhibitory effect on sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists with few cardiovascular side-effects. The initial pharmacological profile of such a group of compounds has recently been disclosed. One of these compounds has been found to be efficacious in the relief of acute attacks of migraine.
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| 14. |
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| 15. |
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| 16. |
- Edvinsson, Lars, et al.
(författare)
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Discovery of CGRP in relation to migraine
- 2019
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 39:3, s. 331-332
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 17. |
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| 18. |
- Edvinsson, Lars, et al.
(författare)
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Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.
- 2010
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 30:10, s. 1233-1240
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.
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| 19. |
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| 20. |
- Edvinsson, Lars
(författare)
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Role of VIP/PACAP in primary headaches.
- 2013
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 33:13, s. 1070-1072
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Tidskriftsartikel (refereegranskat)
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| 21. |
- Edvinsson, Lars, et al.
(författare)
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The blood-brain barrier in migraine treatment.
- 2008
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28, s. 1245-1258
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Tidskriftsartikel (refereegranskat)abstract
- Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access to the central nervous system by diffusion, whereas other substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized arteriography method. The drugs, given both luminally and abluminally, provide important notions regarding antimigraine site of action, probably abluminal to the BBB. The problems with the BBB in animal models designed to study the pathophysiology, acute treatment models and preventive treatments are discussed with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other vascular beds also. We discuss how this can be related to genuine migraine attacks. Our view is that there exists no clear proof of breakdown or leakage of the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB for efficacy.
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| 22. |
- Edvinsson, Lars
(författare)
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Tracing neural connections to pain pathways with relevance to primary headaches.
- 2011
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 31, s. 737-747
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Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms associated with primary headaches are linked to cranial vascular activity and to the central nervous system (CNS). Review: The central projections of sensory nerves from three cranial vessels are described in order to further understand pain mechanisms involved in primary headaches. Tracers that label small and large calibre primary afferent fibres revealed similar distributions for the central terminations of sensory nerves in the superficial temporal artery, superior sagittal sinus and middle meningeal artery. The sensory nerve fibres from the vessels pass through both the trigeminal and rostral cervical spinal nerves and terminate in the ventrolateral part of the C1-C3 dorsal horns and the caudal and interpolar divisions of the spinal trigeminal nucleus. The C-fibre terminations were located mainly in the superficial layers (Rexed laminae I and II), and the Aδ-fibres terminated in the deep layers (laminae III and IV). The rostral projections from the ventrolateral C1-C2 dorsal horn revealed terminations in the medial and lateral parabrachial nuclei, the cuneiform nucleus, the periaqueductal gray, the deep mesencephalic nucleus, the thalamic posterior nuclear group and its triangular part, and the thalamic ventral posteromedial nucleus. The terminations in the pons and midbrain were predominately bilateral, whereas those in the thalamus were confined to the contralateral side. Conclusions: The observations, done in rats with the understanding that similar trigeminovascular organization exists in man, reveal vascular projections into the brainstem and some aspects of the central regions putatively involved in the central processing of noxious craniovascular signals.
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| 23. |
- Edvinsson, M-L, et al.
(författare)
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Comparison of CGRP and NO responses in the human peripheral microcirculation of migraine and control subjects.
- 2008
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Ingår i: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:5, s. 563-566
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Tidskriftsartikel (refereegranskat)abstract
- Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules shown to have a role in migraine pathophysiology. Our objective was to test the hypothesis that migraine subjects are particularly sensitive to these signal molecules. The cutaneous microvascular responses to endothelial and non-endothelial dependent dilators were tested using laser Doppler flowmetry in combination with iontophoresis. The blood flow responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and to local warming (44 degrees C) were compared in this controlled trial. The design was that of two arms: patients diagnosed with migraine without aura (n = 9) for >10 years were compared with nine healthy subjects matched for age and gender (seven female and two male, age range 30-60 years). Iontophoretic administration resulted in local vasodilation. ACh induced a relaxation of 1225 +/- 245% (relative to baseline) in controls and 1468 +/- 368% (P > 0.05) in migraine. The responses to SNP were 873 +/- 193% in controls and 1080 +/- 102% (P > 0.05) in migraine subjects. The responses to CGRP were 565 +/- 89% in controls and 746 +/- 675% (P > 0.05) in migraine patients. The responses to local heating which induced maximum dilation did not differ between the groups (1976 +/- 314% for controls and 1432 +/- 226% in migraine; P > 0.05. We conclude that there is no change in the microvascular responsiveness of the subcutaneous microvasculature in migraine.
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