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3. |
- Edvinsson, Lars
(author)
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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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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 24:8, s. 611-622
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Research review (peer-reviewed)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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4. |
- Edvinsson, Lars, et al.
(author)
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The blood-brain barrier in migraine treatment.
- 2008
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28, s. 1245-1258
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Journal article (peer-reviewed)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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5. |
- Edvinsson, M-L, et al.
(author)
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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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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:5, s. 563-566
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Journal article (peer-reviewed)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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6. |
- Frese, A, et al.
(author)
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Calcitonin gene-related peptide in cervicogenic headache
- 2005
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 25:9, s. 700-703
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Journal article (peer-reviewed)abstract
- Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11 patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference beween CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein. There is no evidence for an activation of the trigeminovascular system in CEH. In certain cases, clinical differentiation between CEH and migraine without aura is difficult. Plasma CGRP levels might serve as a biological marker to distinguish the two headache entities.
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7. |
- Kruuse, C., et al.
(author)
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Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers
- 2010
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 30:4, s. 467-474
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Journal article (peer-reviewed)abstract
- The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 mu g kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 +/- 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 mu g kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P < 0.05), while jugular CGRP-LI levels were unchanged (19.0 +/- 2.8 pmol/l; P > 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.
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8. |
- Liu, Y, et al.
(author)
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Brainstem and thalamic projections from a craniovascular sensory nervous centre in the rostral cervical spinal dorsal horn of rats.
- 2009
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 29, s. 935-948
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Journal article (peer-reviewed)abstract
- To examine the ascending projections from the headache-related trigeminocervical complex in rats, biotinylated dextran amine (BDA) was injected into the ventrolateral dorsal horn of segments C1 and C2, a region previously demonstrated to receive input from sensory nerves in cranial blood vessels. Following injections into laminae I-II, BDA-labelled terminations were found bilaterally in several nuclei in the pons and the midbrain, including the pontine reticular nucleus, the parabrachial nuclei, the cuneiform nucleus and the periaqueductal grey. In the diencephalon, terminations were confined to the contralateral side and evident foremost in the posterior nuclear group, especially its triangular part, and in the ventral posteromedial nucleus. Following injections extending through laminae I-IV, anterograde labelling was more extensive. Some of the above regions are likely to be involved in the central processing of noxious signals of craniovascular origin and therefore putatively involved in mechanisms associated with primary headaches.
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9. |
- Petersen, KA, et al.
(author)
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Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo
- 2005
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 25:6, s. 424-432
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Journal article (peer-reviewed)abstract
- Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-alpha CGRP, rat-beta CGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; E-max for alpha CGRP and beta CGRP were 35 +/- 0.5% and 10.8 +/- 0.2%. These responses were blocked by CGRP(8-37). The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administered alpha CGRP and beta CGRP were compared with pre-infusion baseline. Intravenous infusion of alpha CGRP and beta CGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 +/- 7.5% and 49.1 +/- 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 +/- 3.3 mmHg and 49.2 +/- 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries.
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10. |
- Smith, D, et al.
(author)
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An immunocytochemical investigation of human trigeminal nucleus caudalis: CGRP, substance P and 5-HT1D-receptor immunoreactivities are expressed by trigeminal sensory fibres
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:6, s. 424-431
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Journal article (peer-reviewed)abstract
- 5-HT1D (but not 5-HT1B )-receptor immunoreactivity (i.r.) can be detected on trigeminal fibres within the spinal trigeminal tract of the human brainstem. The present study used immunohistochemical and morphometric techniques to determine the proportions of trigeminal fibres expressing substance P, CGRP or 5-HT1D -receptor immunoreactivities. Co-localization studies between 5-HT1D -receptor and substance P- or CGRP-i.r. were also performed. Brainstem material was obtained with consent (four donors) and the total number of immunoreactive fibres within the trigeminal tract was estimated using random field sampling. A greater proportion of fibres (>1 mum diameter) expressed CGRP-i.r. (80 +/- 6%) compared with substance P-i.r. (46 +/- 7%) or 5-HT1D -receptor-i.r. (25 +/- 1%). 5-HT1D -receptor-i.r. was co-localized on some CGRP- or substance P-i.r. fibres. This suggests that 5-HT1D -receptors can regulate the release of CGRP and substance P and may be relevant to the clinical effectiveness of 5-HT1B/1D -receptor agonists in the treatment of migraine and other cranial pain syndromes.
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11. |
- Tfelt-Hansen, P, et al.
(author)
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Pharmacokinetic and pharmacodynamic variability as possible causes for different drug responses in migraine. A comment
- 2007
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 27:10, s. 1091-1093
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Research review (peer-reviewed)abstract
- The pharmacokinetics of antimigraine drugs zolmitriptan and sumatriptan varied considerably with a fourfold to 10-fold variation in plasma levels. In addition, the pharmacodynamics of triptans as investigated in vitro also varied considerably. In theory, there should probably be a 10-fold variation in doses available, but in clinical practice a fourfold difference in doses will probably cover the needs of most patients.
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12. |
- Uddman, Rolf, et al.
(author)
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Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2.
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:2, s. 112-116
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Journal article (peer-reviewed)abstract
- In migraine and other primary headaches there is a strong vascular component. Besides the trigeminovascular components some of the associated symptoms point to the involvement of brain stem regions. The central limb of the trigeminal vascular pathway is its projection to the trigeminal nucleus caudalis (TNC) and to the C1-C2 levels of the spinal cord. The aim of the present study was to demonstrate the occurrence of some neurotransmitters in these regions in man. In both the TNC and in the Rexed's laminae I and II of the dorsal horns at the C1 and C2 levels there were numerous substance P immunoreactive fibres. Fibres containing calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide (PACAP) were moderately dense in number. Fibres containing vasoactive intestinal peptide (VIP) or nitric oxide synthase (NOS) were not seen in the TNC or at the C1 and C2 levels of the spinal cord.
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13. |
- Tfelt-Hansen, P, et al.
(author)
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Evaluation and registration of adverse events in clinical drug trials in migraine.
- 2008
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 28:7, s. 683-8
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Journal article (peer-reviewed)abstract
- Tolerability of a drug should be regarded as important as its efficacy. In all four phases of drug development evaluation of adverse events is important. Recommendations for assessment of adverse events in acute and prophylactic clinical drug trials in migraine are given. Tolerability may be indirectly assessed using measures of general well-being and eight such tools are presented. Finally, recommendations for reporting of adverse events are given.
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14. |
- Baad-Hansen, L, et al.
(author)
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Effect of systemic monosodium glutamate (MSG) on headache and pericranial muscle sensitivity
- 2010
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 30:1, s. 68-76
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Journal article (peer-reviewed)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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15. |
- Becker, C., et al.
(author)
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Migraine incidence, comorbidity and health resource utilization in the UK
- 2008
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 28:1, s. 57-64
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Journal article (peer-reviewed)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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16. |
- Ekbom, K, et al.
(author)
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Age at onset and sex ratio in cluster headache: observations over three decades
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:2, s. 94-100
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Journal article (peer-reviewed)abstract
- Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male: female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.
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17. |
- Ekbom, K, et al.
(author)
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Periods of cluster headache induced by nitrate therapy and spontaneous remission of angina pectoris during active clusters
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:2, s. 92-98
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Journal article (peer-reviewed)abstract
- Glyceryl trinitrate (GTN) is known to induce single extra attacks of cluster headache (CH) during active cluster periods, most probably via actions of nitric oxide (NO). Induction of whole periods of CH by organic nitrates has, however, attracted little attention in the literature. We report on eight patients with episodic CH and coexistent effort-induced angina pectoris. Cases 1-6 had been free of their headaches for many years but got recurrence of CH within a few weeks after the administration of long-acting organic nitrates (isosorbide-dinitrate, isosorbide-5-mononitrate or slow-release GTN) aimed at treating their chest pains. These nitrate-induced headache periods were more severe and had a longer duration than the previous spontaneous ones. Furthermore, one of the subjects and two additional cases experienced a marked reduction of their anginal attacks during successive CH periods. Exercise time to effort-induced angina was increased in all three patients and one of them revealed a markedly elevated threshold for eliciting ischaemic cardiac symptoms by standardized physical exercise on a cycle ergometer. We hypothesize whether extra CH periods elicited by sustained nitrate therapy and remission of angina pectoris during active clusters are caused by central mechanisms involving inhibition of sympathetic tone and effects on both cranial vessels and cardiac functions.
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18. |
- Ekbom, T, et al.
(author)
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Did Franz Kafka suffer from cluster headache?
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:4, s. 309-311
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Journal article (other academic/artistic)
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19. |
- HANNERZ, J, et al.
(author)
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Effects of increasing the intracranial blood volume in cluster headache patients and controls
- 1995
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 15:6, s. 499-503
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Journal article (peer-reviewed)abstract
- Eleven patients with episodic cluster headache in period, five patients out of period and six controls were studied concerning the effects of an increase of the intracranial blood volume by tilting. Common carotid artery (CCA) blood flow was similar in all three groups at baseline and during tilting. CCA diameters were similar at baseline and increased during tilting in all three groups, indicating that tilting caused an increase in the extra- and intracranial blood volume. Unilateral pain or sympathetic dysfunction did not appear during tilting in the patients out of period or in the controls. In four of eight studied patients with cluster headache in period, unilateral miosis and ptosis appeared during tilting. Two of these four patients developed intense unilateral pain, while the other two did not report any pain. Four other patients developed slight unilateral pain but no sympathetic dysfunction during tilting.
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20. |
- Landtblom, Anne-Marie, 1953-, et al.
(author)
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Sudden onset headache : a prospective study of features, incidence and causes
- 2002
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 22:5, s. 354-360
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Journal article (peer-reviewed)abstract
- Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.
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21. |
- Laurell, Katarina, et al.
(author)
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A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren
- 2006
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 26:7, s. 809-815
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Journal article (peer-reviewed)abstract
- Information is sparse concerning the incidence and prognosis of headache in children from the general population, especially of tension-type headache. In this study, headache diagnoses and symptoms were reassessed in 122 out of 130 schoolchildren after 3 years. Nearly 80% of those with headache at first evaluation still reported headache at follow-up. Although the likelihood of experiencing the same headache diagnosis and symptoms was high, about one-fifth of children with tension-type headache developed migraine and vice versa. Female gender predicted migraine and frequent headache episodes predicted overall headache at follow-up. The estimated average annual incidence was 81 and 65 per 1000 children, for tension-type headache and migraine, respectively. We conclude that there is a considerable risk of developing and maintaining headache during childhood. Headache diagnoses should be reassessed regularly and treatment adjusted. Girls and children with frequent headache have a poorer prognosis and therefore intervention is particularly important in these groups.
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22. |
- Laurell, Katarina, et al.
(author)
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Headache in schoolchildren : agreement between different sources of information
- 2003
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In: Cephalalgia. - : Blackwell Publishing. - 0333-1024 .- 1468-2982. ; 23:6, s. 420-428
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Journal article (peer-reviewed)abstract
- The level of agreement between different sources of information, i.e. questionnaires, interviews and diaries, was evaluated in a sample of 129 schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache diagnoses and headache features showed high agreement between questionnaires and subsequent interviews. The concordance between questionnaires and interviews for headache diagnoses increased, and the number of unclassified headaches decreased, when the International Headache Society (IHS) duration criterion was excluded. When comparing headache frequency reported in questionnaires and interviews with diary recordings, the agreement was low and the frequency higher in the diaries. Overall, the agreement between questionnaires, interviews and diaries was not related to age or gender. The questionnaire may serve as a valid source of information in studies of headache in schoolchildren. Prospective recordings in diaries provide additional information, in particular of low-intensity headache. In children, the IHS duration criterion should be modified or excluded.
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23. |
- Laurell, Katarina, et al.
(author)
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Prevalence of headache in Swedish schoolchildren, with a focus on tension-type headache
- 2004
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In: Cephalalgia. - : Blackwell Publishing. - 0333-1024 .- 1468-2982. ; 24:5, s. 380-388
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Journal article (peer-reviewed)abstract
- To estimate the prevalence of tension-type headache, migraine and other headaches, 1850 schoolchildren, age 7-15 years, from the city of Uppsala, were invited to complete a questionnaire. The response rate was 74.1%. To validate the information from the questionnaires, 131 children and their parents were interviewed. Using the criteria of the International Headache Society, the 1-year prevalence of tension-type headache and migraine was 9.8 and 11.0%, respectively. However, these prevalence rates increased considerably, to 23.0 and 17.0%, respectively, when excluding the criteria defining the number of earlier episodes and duration of headache. The prevalence of headache increased with age, similarly in girls and boys up to 11 years, and thereafter only in girls. The preponderance in teenage girls was even more pronounced for tension-type headache than for migraine. Our results indicate an increase over time in headache prevalence when compared with findings in a study conducted in the same city in 1955.
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24. |
- Linde, Mattias, 1966, et al.
(author)
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Role of the needling per se in acupuncture as prophylaxis for menstrually related migraine: a randomized placebo-controlled study.
- 2005
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 25:1, s. 41-7
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Journal article (peer-reviewed)abstract
- The objectives were to introduce a new method for controlled trials of acupuncture in the field of headache research and to examine the role of needling per se. Women with menstrually related migraine were randomized to three months of treatment with verum or placebo needles. Three standard size casts were moulded to secure the placebo needles in the head. No significant differences were found between the verum group (n=15) and the placebo group (n=13) during treatment or follow up three and six months later, either in the attack frequency or in the number of days per month with migraine, headache intensity or drug-use. The casts held the needles exactly in place despite movements of the head, and are validated as practical, hygienic and extremely durable. This method is satisfactory for controlled studies of acupuncture in headache. It is possible that the positive results in earlier clinical trials on acupuncture in migraine are attributable to other mechanisms than needling of subcutaneous tissue.
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25. |
- Linde, Mattias, 1966, et al.
(author)
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Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.
- 2004
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 24:12, s. 1057-66
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Journal article (peer-reviewed)abstract
- Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.
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26. |
- Mattsson, Peter
(author)
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Mammography-related breast pain is associated with migraine
- 2009
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 29:6, s. 616-623
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Journal article (peer-reviewed)abstract
- There is little information about the perception of experimentally inducedextracephalic pain in migraine. This study investigates the associations between mammography-related pain and migraine. A neurologist clinically assessed 630 women aged 40–74 years attending a population-based breast cancer screening programme. Headache criteria proposed by the International Headache Society were used. Mammography-related pain was measured on a 100-mm visualanalogue scale. High levels of mammography-related pain were associated with migraine. This association was related to mammographic examination during the early follicular phase and menopausal status, but unrelated to differences in age, compression pressure, education, current use of hormonal replacement therapy, anxiety, and recent use of analgesics and antimigraine medication. The results of the present study indicate that migraine and compression-induced breast pain are related.
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27. |
- Mattsson, Peter
(author)
-
Migraine headache and obesity in women aged 40-74 years : A population-based study
- 2007
-
In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 27:8, s. 877-880
-
Journal article (peer-reviewed)abstract
- This study investigates the associations between obesity and migraine. A neurologist clinically assessed 684 women aged 40-74 years attending a population-based mammography screening programme. Body height and weight were measured and body mass index (BMI) calculated. Obesity was defined as a BMI ≥ 30 kg/m2. The proportion of obesity did not differ between women with active migraine, women with inactive migraine or women who had never experienced migraine (P = 0.96). The distribution of frequency, intensity, duration or severity of attacks did not differ between obese and non-obese women with migraine. In this study there were no significant associations between migraine or migraine characteristics on the one hand and obesity on the other.
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28. |
- Meyer, EL, et al.
(author)
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beta-Receptor response to noradrenaline in cluster headache. A study of adipose tissue lipolysis
- 2006
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 26:7, s. 831-836
-
Journal article (peer-reviewed)abstract
- We have previously shown decreased lipolysis in both phases of cluster headache (CH), as an indication of a sympathetic dysregulation. Reduced lipolysis could be a result of diminished β-receptor sensitivity in adipose tissue. The aim of this study was to measure the lipolytic response to noradrenaline in 10 CH patients in remission and in 10 healthy subjects, to estimate β-receptor function. Microdialysis technique was used to measure the increase of glycerol, the end-product of lipolysis, during infusion of noradrenaline into the adipose tissue. Noradrenaline infusion resulted in a distinct elevation of glycerol. The average glycerol increase was significantly higher in CH patients (121± ± 48) than in healthy subjects (77± ± 41) ( P < 0.05), which indicates increased β-receptor response to noradrenaline in CH patients in remission. This may be due to up-regulated β-receptor sensitivity, secondary to reduced sympathetic outflow and a primary autonomic disturbance in CH.
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29. |
- Meyer, EL, et al.
(author)
-
Nocturnal secretion of growth hormone, noradrenaline, cortisol and insulin in cluster headache remission
- 2007
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 27:8, s. 912-919
-
Journal article (peer-reviewed)abstract
- We have previously shown decreased, nocturnal lipolysis in both phases of cluster headache (CH). Lipolysis is stimulated by noradrenaline (NA), growth hormone (GH) and cortisol, and inhibited by insulin, hormones which are directly or indirectly regulated by the hypothalamus. Our aim was to investigate the nocturnal secretion of NA, GH, cortisol and insulin in nine CH patients in remission and 10 healthy controls. Nocturnal venous blood samples were collected in hourly intervals for analysis of NA, cortisol and insulin and in 30-min intervals for GH. We found a reduced increase in GH between 24.00 h and 01.00 h (ANOVA, P < 0.05) in CH patients. Nocturnal secretion of NA, cortisol and insulin did not differ significantly between the groups. The altered nocturnal GH pattern that was seen in CH patients in remission might in part explain the altered nocturnal lipolysis previously found and further indicate a permanent hypothalamic disturbance in CH.
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30. |
- Olesen, J, et al.
(author)
-
Funding of headache research in Europe
- 2007
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 27:9, s. 995-999
-
Journal article (peer-reviewed)abstract
- Migraine costs European Society ¬27 billion per year. Other headaches may account for a similar amount. Given this enormous impact, the question arises as to whether the funding of research efforts in this field are sufficient. A recent European study called the Resource Allocation to Brain Research in Europe (RABRE) examined funding of brain research. Identified charities and Government agencies in Europe filled out a questionnaire regarding their funding of brain diseases. Industry spending was evaluated by three different previously validated methods. In the present report, detailed results are presented for migraine and other headaches. In 2004, migraine research was funded by nearly €315 million. Of this, €308 million was invested by the pharmaceutical industry, whereas public funding was estimated at €7 million. No funding was identified for non-migraine headache disorders. Of the public spending, €714 000 came from private foundations. There was a very large difference between different European countries in the funding of headache research. When public funding was compared with the cost of different brain disorders, migraine funding was in the middle range. This was due to relatively large industry funding. Compared with societal costs, migraine received the least public funds amongst all brain disorders, i.e. 0.025%. We conclude that migraine attracts reasonable interest from the pharmaceutical industry, but Governmental and charity funding is extremely low and no funding was identified for non-migraine headache disorders. Considering the huge economic impact of these disorders, public funding of research into migraine and other headaches should be greatly increased in the future.
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31. |
- Ramsberg, Joakim, et al.
(author)
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The cost-effectiveness of oral triptan therapy in Sweden
- 2007
-
In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 27:1, s. 54-62
-
Journal article (peer-reviewed)abstract
- The literature suggests that triptans are cost effective compared with older types of migraine treatment. However, which of the triptans that is most cost effective has not been established. We compared the costs and effects of triptan treatment from a Swedish societal perspective, using evidence from the literature. A probabilistic cost-effectiveness model was constructed to investigate the costs and effects of treating a single attack in a typical migraine patient. The end-point used in the base-case analysis was sustained pain free without any adverse events (SNAE). We searched the scientific literature for meta-analyses reporting the efficacy of oral triptans. All treatments except rizatriptan 10 mg and eletriptan 40 mg were dominated. The incremental cost per SNAE of rizatriptan 10 mg compared with eletriptan 40 mg was approximately €100. There was substantial uncertainty concerning the results, but probabilistic analysis showed that rizatriptan 10 mg and eletriptan 40 mg had the highest probability of being cost-effective. © Blackwell Publishing Ltd.
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32. |
- Remahl, AIMN, et al.
(author)
-
Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study
- 2002
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:9, s. 730-739
-
Journal article (peer-reviewed)abstract
- Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by > 50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.
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33. |
- Remahl, AIMN, et al.
(author)
-
Placebo response in cluster headache trials: a review
- 2003
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 23:7, s. 504-510
-
Journal article (peer-reviewed)abstract
- Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the pain, the placebo response in CH has been considered to be small. During the eighties the first double-blind, placebo-controlled trials were reported, and placebo responses demonstrated. Here we review the placebo response in CH trials in order to assess its magnitude and consider how future studies can be optimized. Six trials were identified with a double-blind, placebo-controlled, cross-over design testing treatments of acute CH. For those with a primary endpoint set to no or mild headache the placebo responses varied from 7 to 42%. In five of seven prophylactic trials, using a double-blind, placebo-controlled, parallel-group design, the placebo was merely used to set a baseline for comparison. The placebo responses were reported in only two trials. Here the response varies from 14 to 43%, the lowest value was reported using the strict endpoint; cessation of headache attacks. We conclude that a placebo response exists in trials of drugs on CH patients. Furthermore, this placebo response is of the same magnitude as that seen in migraine studies. We recommend the use of IHS guidelines when designing new trials. The possibility of a genuine biological mechanism responsible for the placebo response is discussed.
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34. |
- Shepheard, S, et al.
(author)
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Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370
- 1999
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 19:10, s. 851-858
-
Journal article (peer-reviewed)abstract
- This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10−5 M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg−1, iv) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg−1, iv) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg−1, iv), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg−1, iv. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.
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35. |
- Sjostrand, C, et al.
(author)
-
Analysis of nitric oxide synthase genes in cluster headache
- 2002
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 22:9, s. 758-764
-
Journal article (peer-reviewed)abstract
- The aetiology of cluster headache is still not yet completely understood, but the potential relevance of genetic factors has been recognized during recent years. Nitric oxide (NO) plays a critical role in the regulation of vasodilation, neurotransmission, inflammation and many other events throughout the body. NO also appears to be an important mediator of vascular headache pathophysiology. In this study we have performed an association analysis of five polymorphic micro-satellite markers in the three different NO synthase (NOS) genes; nNOS (NOS1), iNOS (NOS2A) and eNOS (NOS3). Ninety-one cluster headache patients diagnosed according to International Headache Society criteria and 111 matched controls were studied. Phenotype and allele frequencies were similarly distributed in patients and controls except for an iNOS (NOS2A) pentanucleotide repeat allele which was significantly more common in controls. We observed a higher phenotype frequency of this allele in our control group compared with rates in control groups of other studies, whereas the frequency in our patients was similar to that in controls from previous reports. Thus, we conclude that it is unlikely that genetic variations within the NOS genes contribute greatly to cluster headache susceptibility.
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36. |
- Sjostrand, C, et al.
(author)
-
CACNA1A gene polymorphisms in cluster headache
- 2001
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 21:10, s. 953-958
-
Journal article (peer-reviewed)abstract
- Cluster headache (CH) is a primary headache disorder where the aetiological and pathophysiological mechanisms still are largely unknown. An increased risk of CH in first- and second-degree relatives suggests the importance of genetic factors. Mutations of the P/Q type calcium channel alpha 1 subunit (CACNA1A) gene on chromosome 19p13 have been shown to cause several neurological disorders with a wide clinical spectrum, mainly episodic diseases. Missence mutations of the gene cause familial hemiplegic migraine (FHM) and it is also likely to be involved in the more common forms of migraine. The CACNA1A gene is thus a promising candidate gene for CH. In this study we performed an association analysis of an intragenic polymorphic (CA)n-repeat with marker D19S1150 and a (CAG)n-repeat in the 3′UTR region, in 75 patients with CH according to IHS criteria and 108 matched controls. Genotypes and allele frequencies were similarly distributed in patients and controls. Linkage disequilibrium between the two markers was similar in patients and controls. We conclude that an importance of the CACNA1A gene in sporadic CH is unlikely.
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37. |
- Sjostrand, C, et al.
(author)
-
Familial cluster headache. Is atypical cluster headache in family members part of the clinical spectrum?
- 2005
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 25:11, s. 1068-1077
-
Journal article (peer-reviewed)abstract
- Familial cluster headache (CH) was analysed in 21 Swedish families. Diagnosis was made according to The International Classification of Headache Disorders 2004. We identified 55 affected, of whom 42 had episodic or chronic CH, one had probable CH and 12 had atypical symptoms. The atypical cases did not fulfil the diagnostic criteria for CH, but had clinical symptoms with more resemblance to CH than to migraine or other trigeminal autonomic cephalgia syndromes. The overall male : female ratio was 1.8 : 1. The overall mean age at onset was significantly lower in the second/third generation than in the first generation (mean age at onset 22 vs. 31 years, SD ± 7 vs. 13 years; P < 0.01). This may be anticipation or selection bias, since individuals with late age at onset from the second/third generation may not yet have symptoms. The prevalence of migraine was 24% (13/55), i.e. similar to the prevalence in the general population. The high incidence of atypical CH cases in the Swedish families with other members affected with CH may suggest that the spectrum of CH is broader than previously thought. We suggest that atypical CH in CH families may represent an expanded spectrum of the disease with a common aetiology, i.e. a common genetic background.
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38. |
- Svensson, DA, et al.
(author)
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A note on cluster headache in a population-based twin register
- 2003
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 23:5, s. 376-380
-
Journal article (peer-reviewed)abstract
- Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.
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39. |
- Svensson, DA, et al.
(author)
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Genetic and environmental influences on recurrent headaches in eight to nine-year-old twins
- 1999
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 19:10, s. 866-872
-
Journal article (peer-reviewed)abstract
- The major objective of the present study was to estimate genetic and environmental influences on recurrent headaches in prepubescent twins. A nationwide cohort of 8 to 9-year-old Swedish twins ( n = 1,480) was screened for nonsymptomatic and recurrent headaches through a questionnaire mailed to their parents (75% response frequency). Among positives, 79% of headaches were classified as migraine or tension-type headache in close accordance with the International Headache Society criteria. The prevalences of migraine and nonmigrainous headaches were 2.4% and 11.3%, respectively, and without significant differences between the sexes or zygosity types. Inheritance on liability to recurrent headaches was estimated to 70% (a2 = 0.70, 95% CI = 0.54 − 0.82) for boys and girls but the genetic effect was found to be uncorrelated between the sexes. We conclude that genetic and individual specific effects are important for recurrent headaches of migrainous and nonmigrainous types in prepubescent children, and that different genetic etiologies might exist for boys and girls.
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40. |
- Söderberg, Elisabeth, et al.
(author)
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Chronic tension-type headache treated with acupuncture, physical training and relaxation training. Between-group differences.
- 2006
-
In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 0333-1024. ; 26:11, s. 1320-9
-
Journal article (peer-reviewed)abstract
- The aim of this study was to compare acupuncture, relaxation training and physical training in the treatment of chronic tension-type headache (CTTH). The study comprised 90 consecutive patients with CTTH who were randomly allocated to acupuncture, relaxation training or physical training. Headache intensity, headache-free days and headache-free periods were registered using a visual analogue scale and a headache diary. The measurements were made 4 weeks before, immediately after, and 3 and 6 months after the treatment period. Immediately after the last treatment, the number of headache-free periods and of headache-free days was higher in the relaxation group compared with the acupuncture group. There were no other significant differences between the groups at any time point. The clinical implications of our findings are that relaxation training induced the most pronounced effects directly after the treatment period, compared with acupuncture and physical training.
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41. |
- Varkey, Emma, et al.
(author)
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Physical activity and headache: results from the Nord-Trondelag Health Study (HUNT)
- 2008
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 2008;28:12, s. 1292-1297
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate, using a prospective and a cross-sectional design, the relationship between level of physical activity and migraine and non-migraine headache. In the prospective part, 22 397 participants, not likely to have headache, answered questions about physical activity at baseline (19841986) and responded to a headache questionnaire at follow-up. In the cross-sectional part (1995-1997), 46 648 participants answered questions about headache and physical activity. Physically inactive individuals at baseline were more likely than active individuals to have non-migraine headache 11 years later (odds ratio 1.14, 95± confidence interval 1.02, 1.28). In the cross-sectional analyses, low physical activity was associated with higher prevalence of migraine and non-migraine headache. In both headache groups, there was a strong linear trend ( P< 0.001) of higher prevalence of ‘low physical activity’ with increasing headache frequency. The result may indicate that physical inactivity among headache-free individuals is a risk factor for non-migraine headache and that individuals with headache are less physically active than those without headache.
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42. |
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43. |
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44. |
- Belin, AC
(author)
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Board Walk - January 2022
- 2022
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 42:1, s. 87-
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Journal article (peer-reviewed)
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45. |
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46. |
- Edvinsson, Jacob Carl Alexander, et al.
(author)
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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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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:12, s. 1296-1309
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Journal article (peer-reviewed)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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47. |
- Edvinsson, Lars, et al.
(author)
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Discovery of CGRP in relation to migraine
- 2019
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 39:3, s. 331-332
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Journal article (other academic/artistic)
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48. |
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49. |
- Edvinsson, Lars, et al.
(author)
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Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.
- 2010
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 30:10, s. 1233-1240
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Journal article (peer-reviewed)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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50. |
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