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1.
  • Affatato, Oreste, et al. (författare)
  • Major sex differences in migraine prevalence among occupational categories : a cross-sectional study using UK Biobank
  • 2021
  • Ingår i: Journal of Headache and Pain. - : Springer Nature. - 1129-2369 .- 1129-2377. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Migraine represents one of the most prevalent neurological conditions worldwide. It is a disabling condition with high impact on the working situation of migraineurs. Interestingly, gender-related differences regarding an association of migraine with important occupational characteristics has been hardly studied. Methods The current study scrutinizes gender-specific differences in the prevalence of migraine across a broad spectrum of occupational categories, shedding also light on associations with important job-related features such as shift work, job satisfaction, and physical activity. The study included data from 415 712 participants from the UK Biobank cohort, using the official ICD10 diagnosis of migraine and other health conditions as selection criteria. Prevalence ratios of migraineurs compared to healthy controls among different occupational categories and job-related variables were estimated using log-binomial regression analyses. Statistical models were adjusted for important sociodemographic features such as age, BMI, ethnicity, education and neuroticism. To better highlight specific differences between men and women we stratified by sex. Results We detected a differential prevalence pattern of migraine in relation to different job categories between men and women. Especially in men, migraine appears to be more prevalent in highly physically demanding occupations (PR 1.38, 95% CI [0.93, 2.04]). Furthermore, migraine is also more prevalent in jobs that frequently involve shift or night shift work compared to healthy controls. Interestingly, this prevalence is especially high in women (shift work PR 1.45, 95% CI [1.14, 1.83], night shift work PR 1.46, 95% CI [0.93, 2.31]). Conclusion Our results show that migraine is genderdependently associated with physically demanding jobs and shift working.
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  • Christensen, R. H., et al. (författare)
  • Imaging the inflammatory phenotype in migraine
  • 2022
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing. We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5). In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.
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  • Christiansen, Isabella Mai, et al. (författare)
  • Dual action of the cannabinoid receptor 1 ligand arachidonyl-2′-chloroethylamide on calcitonin gene-related peptide release
  • 2022
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Based on the current understanding of the role of neuropeptide signalling in migraine, we explored the therapeutic potential of a specific cannabinoid agonist. The aim of the present study was to examine the effect of the synthetic endocannabinoid (eCB) analogue, arachidonyl-2′-chloroethylamide (ACEA), on calcitonin gene-related peptide (CGRP) release in the dura and trigeminal ganglion (TG), as cannabinoids are known to activate Gi/o-coupled cannabinoid receptors type 1 (CB1), resulting in neuronal inhibition. Methods: The experiments were performed using the hemi-skull model and dissected TGs from male Sprague-Dawley rats. CGRP release was induced by either 60 mM K+ (for depolarization-induced stimulation) or 100 nM capsaicin (for transient receptor potential vanilloid 1 (TRPV1) -induced stimulation) and measured using an enzyme-linked immunosorbent assay. The analysis of CGRP release data was combined with immunohistochemistry in order to study the cellular localization of CB1, cannabinoid receptor type 2 (CB2), CGRP and receptor activity modifying protein 1 (RAMP1), a subunit of the functional CGRP receptor, in the TG. Results: CB1 was predominantly expressed in neuronal somas in which colocalization with CGRP was observed. Furthermore, CB1 exhibited colocalization with RAMP1 in neuronal Aδ-fibres but was not clearly expressed in the CGRP-immunoreactive C-fibres. CB2 was mainly expressed in satellite glial cells and did not show substantial colocalization with either CGRP or RAMP1. Without stimulation, 140 nM ACEA per se caused a significant increase in CGRP release in the dura but not TG, compared to vehicle. Furthermore, 140 nM ACEA did not significantly modify neither K+- nor capsaicin-induced CGRP release. However, when the TRPV1 blocker AMG9810 (1 mM) was coapplied with ACEA, K+-induced CGRP release was significantly attenuated in the TG and dura. Conclusions: Results from the present study indicate that ACEA per se does not exhibit antimigraine potential due to its dual agonistic properties, resulting in activation of both CB1 and TRPV1, and thereby inhibition and stimulation of CGRP release, respectively.
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  • Csáti, A, et al. (författare)
  • Kynurenic acid modulates experimentally induced inflammation in the trigeminal ganglion.
  • 2015
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 16:99
  • Tidskriftsartikel (refereegranskat)abstract
    • The trigeminal ganglion (TG) plays a central role in cranial pain. Administration of complete Freund's adjuvant (CFA) into the temporomandibular joint (TMJ) elicits activation of TG. Kynurenic acid (KYNA) is an endogenous excitatory amino acid receptor blocker, which may have an anti-inflammatory effect. We hypothesize that KYNA may reduce CFA-induced activation within the TG.
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  • Dawson, Andreas, et al. (författare)
  • Dopamine in plasma : a biomarker for myofascial TMD pain?
  • 2016
  • Ingår i: Journal of Headache and Pain. - : Springer. - 1129-2369 .- 1129-2377. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dopaminergic pathways could be involved in the pathophysiology of myofascial temporomandibular disorders (M-TMD). This study investigated plasma levels of dopamine and serotonin (5-HT) in patients with M-TMD and in healthy subjects. METHODS: Fifteen patients with M-TMD and 15 age- and sex-matched healthy subjects participated. The patients had received an M-TMD diagnosis according to the Research Diagnostic Criteria for TMD. Perceived mental stress, pain intensity (0-100-mm visual analogue scale), and pressure pain thresholds (PPT, kPa) over the masseter muscles were assessed; a venous blood sample was taken. RESULTS: Dopamine in plasma differed significantly between patients with M-TMD (4.98 ± 2.55 nM) and healthy controls (2.73 ± 1.24 nM; P < 0.01). No significant difference in plasma 5-HT was observed between the groups (P = 0.75). Patients reported significantly higher pain intensities (P < 0.001) and had lower PPTs (P < 0.01) compared with the healthy controls. Importantly, dopamine in plasma correlated significantly with present pain intensity (r = 0.53, n = 14, P < 0.05) and perceived mental stress (r = 0.34, n = 28, P < 0.05). CONCLUSIONS: The results suggest that peripheral dopamine might be involved in modulating peripheral pain. This finding, in addition to reports in other studies, suggests that dopaminergic pathways could be implicated in the pathophysiology of M-TMD but also in other chronic pain conditions. More research is warranted to elucidate the role of peripheral dopamine in the pathophysiology of chronic pain.
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  • Deen, Marie, et al. (författare)
  • Blocking CGRP in migraine patients – a review of pros and cons
  • 2017
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18, s. 1-9
  • Forskningsöversikt (refereegranskat)abstract
    • Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: small molecule CGRP receptor antagonists (gepants), and monoclonal antibodies, targeting either CGRP or the CGRP receptor. Several trials have been conducted to test the efficacy and safety of these drugs. In general, a superior efficacy compared to placebo has been shown, especially with regards to the antibodies. In addition, the efficacy is in line with other currently used prophylactic treatments. The drugs have also been well tolerated, except for some of the gepants, which induced a transient increase in transaminases. Thus, blocking CGRP in migraine patients is seemingly both efficient and well tolerated. However, CGRP and its receptor are abundantly present in both the vasculature, and in the peripheral and central nervous system, and are involved in several physiological processes. Therefore, blocking CGRP may pose a risk in subjects with comorbidities such as cardiovascular diseases. In addition, long-term effects are still unknown. Evidence from animal studies suggests that blocking CGRP may induce constipation, affect the homeostatic functions of the pituitary hormones or attenuate wound healing. However, these effects have so far not been reported in human studies. In conclusion, this review suggests that, based on current knowledge, the pros of blocking CGRP in migraine patients exceeds the cons.
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  • Edvardsson, Bengt, et al. (författare)
  • Cerebral infarct presenting with thunderclap headache.
  • 2009
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 10, s. 207-209
  • Tidskriftsartikel (refereegranskat)abstract
    • A 73-year-old man presented with a thunderclap headache (TCH), suggesting a subarachnoid haemorrhage. Neurological examination, computer tomography of the head, and cerebrospinal fluid examination were normal. Magnetic resonance imaging of the brain revealed a supratentorial cerebral infarct. No cerebral aneurysm could be detected. A TCH can be the presenting feature of many conditions. A formula for the diagnostic assessment of TCH should be established. The management of this type of headache is controversial. Articles differ in their conclusions and recommendations. An expansion of routine investigations should be performed in cases where the neurological examination, cerebrospinal fluid analysis, and computer tomography are normal. A TCH can be the primary clinical feature of a supratentorial cerebral infarct.
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  • Edvardsson, Bengt, et al. (författare)
  • Reversible cerebral vasoconstriction syndrome associated with autonomic dysreflexia.
  • 2010
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 11, s. 277-280
  • Tidskriftsartikel (refereegranskat)abstract
    • A 32-year-old man with a residual spastic quadriparesis from a traumatic C5-C6 fracture experienced a severe thunderclap headache. The medical history revealed an episode of autonomic dysreflexia (AD) due to neurogenic bladder/urinary tract infection (UTI). Blood pressure monitoring at admission revealed hypertension; blood pressure reaching 160/100 mmHg (average blood pressure in these patients and also in this patient being 90/60 mmHg). CT scan of the head, cerebrospinal fluid examination, CT angiography and MR angiography of the brain vessels were normal. Another UTI and a subsequent spell of AD were diagnosed. The patient continued to experience recurrent thunderclap headaches. Selective catheter cerebral angiography revealed multiple calibre changes in the intracranial blood vessels. A diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) due to AD was considered. A magnetic resonance imaging (MRI) of the brain after 2 weeks revealed ischaemic changes in the left hemisphere. Follow-up brain MRI after 3 weeks showed reduction in size of the ischaemic changes, and catheter angiography after 6 weeks demonstrated improvement/normalization. A diagnosis of RCVS could be established. Repeated MRI/CT of the brain after 6 months demonstrated a large infarction in the left hemisphere. RCVS has been reported to occur in various clinical settings. It can occur in the setting of AD in patients with traumatic cervical cord injury. Prompt recognition of RCVS may be of vital importance to avoid further morbidity in patients with spinal cord injury.
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  • Edvinsson, Jacob C.A., et al. (författare)
  • C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system
  • 2019
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Monoclonal antibodies (mAbs) towards CGRP or the CGRP receptor show good prophylactic antimigraine efficacy. However, their site of action is still elusive. Due to lack of passage of mAbs across the blood-brain barrier the trigeminal system has been suggested a possible site of action because it lacks blood-brain barrier and hence is available to circulating molecules. The trigeminal ganglion (TG) harbors two types of neurons; half of which store CGRP and the rest that express CGRP receptor elements (CLR/RAMP1). METHODS: With specific immunohistochemistry methods, we demonstrated the localization of CGRP, CLR, RAMP1, and their locations related to expression of the paranodal marker contactin-associated protein 1 (CASPR). Furthermore, we studied functional CGRP release separately from the neuron soma and the part with only nerve fibers of the trigeminal ganglion, using an enzyme-linked immunosorbent assay. RESULTS: Antibodies towards CGRP and CLR/RAMP1 bind to two different populations of neurons in the TG and are found in the C- and the myelinated Aδ-fibers, respectively, within the dura mater and in trigeminal ganglion (TG). CASPR staining revealed paranodal areas of the different myelinated fibers inhabiting the TG and dura mater. Double immunostaining with CASPR and RAMP1 or the functional CGRP receptor antibody (AA58) revealed co-localization of the two peptides in the paranodal region which suggests the presence of the CGRP-receptor. Double immunostaining with CGRP and CASPR revealed that thin C-fibers have CGRP-positive boutons which often localize in close proximity to the nodal areas of the CGRP-receptor positive Aδ-fibers. These boutons are pearl-like synaptic structures, and we show CGRP release from fibers dissociated from their neuronal bodies. In addition, we found that adjacent to the CGRP receptor localization in the node of Ranvier there was PKA immunoreactivity (kinase stimulated by cAMP), providing structural possibility to modify conduction activity within the Aδ-fibers. CONCLUSION: We observed a close relationship between the CGRP containing C-fibers and the Aδ-fibers containing the CGRP-receptor elements, suggesting a point of axon-axon interaction for the released CGRP and a site of action for gepants and the novel mAbs to alleviate migraine.
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  • Edvinsson, Jacob C.A., et al. (författare)
  • MERTK in the rat trigeminal system : a potential novel target for cluster headache?
  • 2024
  • Ingår i: Journal of Headache and Pain. - 1129-2369 .- 1129-2377. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The trigeminal system is key to the pathophysiology of migraine and cluster headache, two primary headache disorders that share many features. Recently, MER proto-oncogene tyrosine kinase (MERTK), a cell surface receptor, was strongly associated with cluster headache through genetic studies. Further, the MERTK ligand galectin-3 has been found to be elevated in serum of migraine patients. In this study, MERTK and MERTK ligands were investigated in key tissue to better understand their potential implication in the pathophysiology of primary headache disorders. Immunohistochemistry was used to map MERTK and galectin-3 expression in rat trigeminal ganglia. RT-qPCR was used to assess MERTK gene expression in blood, and ELISA immunoassays were used for MERTK ligand quantification in serum from study participants with and without cluster headache. MERTK gene expression was elevated in blood samples from study participants with cluster headache compared to controls. In addition, MERTK ligand galectin-3 was found at increased concentration in the serum of study participants with cluster headache, whereas the levels of MERTK ligands growth arrest specific 6 and protein S unaffected. MERTK and galectin-3 were both expressed in rat trigeminal ganglia. Galectin-3 was primarily localized in smaller neurons and to a lesser extent in C-fibres, while MERTK was found in satellite glia cells and in the outer membrane of Schwann cells. Interestingly, a strong MERTK signal was found specifically in the region proximal to the nodes of Ranvier. The overexpression of MERTK and galectin-3 in tissue from study participants with cluster headache, as well as the presence of MERTK in rat peripheral satellite glia cells and Schwann cells in the trigeminal ganglia, further highlights MERTK signalling as an interesting potential future therapeutic target in primary headache. Graphical Abstract: (Figure presented.)
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  • Edvinsson, Lars, et al. (författare)
  • PACAP and its role in primary headaches
  • 2018
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 19:1
  • Forskningsöversikt (refereegranskat)abstract
    • Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide implicated in a wide range of functions, such as nociception and in primary headaches. Regarding its localization, PACAP has been observed in the sensory trigeminal ganglion (TG), in the parasympathetic sphenopalatine (SPG) and otic ganglia (OTG), and in the brainstem trigeminocervical complex. Immunohistochemistry has shown PACAP-38 in numerous cell bodies of SPG/OTG, co-stored with vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and, to a minor degree, with choline acetyltransferase. PACAP has in addition been found in a subpopulation of calcitonin gene-related peptide (CGRP)-immunoreactive cells in the trigeminal system. The PACAP/VIP receptors (PAC1, VPAC1, and VPAC2) are present in sensory neurons and in vascular smooth muscle related to the trigeminovascular system. It is postulated that PACAP is involved in nociception. In support, abolishment of PACAP synthesis or reception leads to diminished pain responses, whereas systemic PACAP-38 infusion triggers pain behavior in animals and delayed migraine-like attacks in migraine patients without marked vasodilatory effects. In addition, increased plasma levels have been documented in acute migraine attacks and in cluster headache, in accordance with findings in experimental models of trigeminal activation. This suggest that the activation of the trigeminal system may result in elevated venous levels of PACAP, a change that can be reduced when headache is treated. The data presented in this review indicate that PACAP and its receptors may be promising targets for migraine therapeutics.
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  • Erdling, André, et al. (författare)
  • Differential inhibitory response to telcagepant on αCGRP induced vasorelaxation and intracellular Ca2+ levels in the perfused and non-perfused isolated rat middle cerebral artery
  • 2017
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Calcitonin gene-related peptide (CGRP) is one of the most potent endogenous vasodilators identified to date. The present study elucidates the differential interaction of CGRP, its receptor and the effect of the CGRP-receptor antagonist telcagepant on intracellular Ca2+ -levels and tension in rat middle cerebral arteries (MCA) by pressurized arteriography, FURA-2/wire myography and immunohistochemistry. Methods: A pressurized arteriograph system was used to evaluate changes in MCA tension when subjected to CGRP and/or telcagepant. Intracellular calcium levels were evaluated using a FURA-2/wire myograph system. Localization of the CGRP-receptor components was verified using immunohistochemistry. Results: Abluminal but not luminal αCGRP (10-12-10-6 M) caused concentration-dependent vasorelaxation in rat MCA. Luminal telcagepant (10-6 M) failed to inhibit this relaxation, while abluminal telcagepant inhibited the relaxation (10-6 M). Using the FURA-2 method in combination with wire myography we observed that αCGRP reduced intracellular calcium levels and in parallel the vascular tone. Telcagepant (10-6 M) inhibited both vasorelaxation and drop in intracellular calcium levels. Both functional components of the CGRP receptor, CLR (calcitonin receptor-like receptor) and RAMP1 (receptor activity modifying peptide 1) were found in the smooth muscle cells but not in the endothelial cells of the cerebral vasculature. Conclusions: This study thus demonstrates the relaxant effect of αCGRP on rat MCA. The vasorelaxation is associated with a simultaneous decrease in intracellular calcium levels. Telcagepant reduced relaxation and thwarted the reduction in intracellular calcium levels localized in the vascular smooth muscle cells. In addition, telcagepant may act as a non-competitive antagonist at concentrations greater than 10-8 M.
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  • Grände, Gustaf, et al. (författare)
  • Comparison of the vasodilator responses of isolated human and rat middle meningeal arteries to migraine related compounds
  • 2014
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Migraine attacks occur spontaneously in those who suffer from the condition, but migraine-like attacks can also be induced artificially by a number of substances. Previously published evidence makes the meninges a likely source of migraine related pain. This article investigates the effect of several vasodilators on meningeal arteries in order to find a connection between the effect of a substance on a meningeal vessel and its ability to artificially induce migraine. A myograph setup was used to test the vasodilator properties of the substances acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil, prostaglandin E-2 (PGE(2)), pituitary adenylate cyclase activating peptide-38 (PACAP-38), calcitonin gene-related peptide (CGRP) and NaCl buffer on meningeal arteries from human and rat. An unpaired t-test was used to statistically compare the mean E-max(%) at the highest concentration of each substance to the E-max(%) of NaCl buffer. In the human experiments, all substances except PACAP-38 had an E-max (%) higher than the NaCl buffer, but the difference was only significant for SNP and CGRP. For the human samples, clinically tested antimigraine compounds (sumatriptan, telcagepant) were applied to the isolated arteries, and both induced a significant decrease of the effect of exogenously administrated CGRP. In experiments on rat middle meningeal arteries, pre-contracted with PGF(2 alpha), similar tendencies were seen. When the pre-contraction was switched to K+ in a separate series of experiments, CGRP and sildenafil significantly relaxed the arteries. Still no definite answer can be given as to why pain is experienced during an attack of migraine. No clear correlation was found between the efficacy of a substance as a meningeal artery vasodilator in human and the ability to artificially induce migraine or the mechanism of action. Vasodilatation could be an essential trigger, but only in conjunction with other unknown factors. The vasculature of the meninges likely contributes to the propagation of the migrainal cascade of symptoms, but more research is needed before any conclusions can be drawn about the nature of this contribution.
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  • Guido, Davide, et al. (författare)
  • Pain rates in general population for the period 1991-2015 and 10-years prediction : results from a multi-continent age-period-cohort analysis
  • 2020
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. Methods We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content self-reported pain experienced at the time of the interview, with a dichotomous (yes or no) modality. Results Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. Conclusions Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.
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  • Hadjikhani, Nouchine, 1966, et al. (författare)
  • Neuroimaging clues of migraine aura
  • 2019
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 20
  • Forskningsöversikt (refereegranskat)abstract
    • While migraine headaches can be provoked, or predicted by the presence of an aura or premonitory symptoms, the prediction or elicitation of the aura itself is more problematic. Therefore, imaging studies directly examining the aura phenomenon are sparse. There are however interictal imaging studies that can shed light on the pathophysiology of the migraine with aura (MWA) cascade. Here, we review findings pointing to the involvement of cortical spreading depression (CSD) and neuroinflammation in MWA. Whether asymptomatic CSD also happens in some migraine without aura is still under debate. In addition, new evidence points to glial activation in MWA, indicating the involvement of astrocytes in the neuroinflammatory cascade that follows CSD, as well as dural macrophages, supporting the involvement of the trigeminovascular system in migraine pain.
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24.
  • Islamoska, Sabrina, et al. (författare)
  • Mid- to late-life migraine diagnoses and risk of dementia : a national register-based follow-up study
  • 2020
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies found an association between migraine and dementia, which are two leading causes of disability. However, these studies did not differentiate between migraine types and did not investigate all prevalent dementia subtypes. The main objective of this national register-based study was to investigate whether migraine was a risk factor for dementia. Additionally, we explored potential differences in dementia risk for migraine with and without aura.Methods: We obtained data on birth cohorts born between 1935 and 1956 (n = 1,657,890) from Danish national registers. Individuals registered with migraine before age 59 (n = 18,135) were matched (1:5) on sex and birthdate with individuals without migraine (n = 1,378,346). Migraine was defined by International Classification of Diseases (ICD) diagnoses and dementia was defined by ICD diagnoses and anti-dementia medication. After matching, 62,578 individuals were eligible for analysis. For the statistical analyses, we used Cox regression models and adjusted for socio-demographic factors and several psychiatric and somatic morbidities.Results: During a median follow-up time of 6.9 (IQR: 3.6-11.2) years, 207 individuals with migraine developed dementia. Compared with individuals without migraine, we found a 50% higher rate of dementia among individuals with migraine (HR = 1.50; 95% CI: 1.28-1.76). Individuals without aura had a 19% higher rate of dementia (HR = 1.19; 95% CI: 0.84-1.70), and individuals with aura had a two times higher rate of dementia (HR = 2.11; 95% CI: 1.48-3.00).Conclusions: Our findings support the hypothesis that migraine is a midlife risk factor for dementia in later life. The higher rate of dementia in individuals with a hospital-based diagnosis of migraine with aura emphasizes the need for studies on pathological mechanisms and potential preventative measures. Furthermore, given that only hospital-based migraine diagnoses were included in this study, future research should also investigate migraine cases derived from the primary healthcare system to include less severe migraine cases.
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  • Jasim, Hajer, et al. (författare)
  • Altered levels of salivary and plasma pain related markers in temporomandibular disorders
  • 2020
  • Ingår i: Journal of Headache and Pain. - : BMC. - 1129-2369 .- 1129-2377. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Different pain syndromes may be characterized by different profiles of mediators reflecting pathophysiological differences, and these alterations may be measured in a simple saliva sample. The aims of the current study were to compare concentration of glutamate, serotonin (5-HT), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and substance P (SP) in saliva and plasma from a well-defined group of patients with chronic temporomandibular disorders myalgia (TMD-myalgia) with a group of pain-free controls, and further investigate the relationship between these markers and clinical characteristics. Methods Patients diagnosed according to the diagnostic criteria for TMD (n = 39), and matched healthy pain-free controls (n = 39) were included. Stimulated whole saliva and plasma samples were collected in the morning. Glutamate was analysed using a colorimetric assay, and 5-HT and SP were analysed by commercially available ELISA. Levels of NGF and BDNF were determined using multiplex electrochemiluminescence assay panel. Results Patients expressed higher salivary and plasma levels of glutamate (saliva: 40.22 +/- 13.23 mu mol/L; plasma: 30.31 +/- 18.73 mu mol/L) than controls (saliva: 33.24 +/- 11.27 mu mol/L; plasma: 20.41 +/- 15.96 mu mol/L) (p < 0.05). Salivary NGF (0.319 +/- 0.261 pg/ml) and BDNF (3.57 +/- 1.47 pg/ml) were lower in patients compared to controls (NGF: 0.528 +/- 0.477 pg/ml; BDNF 4.62 +/- 2.51 pg/ml)(ps < 0.05). Contrary, plasma BDNF, was higher in patients (263.33 +/- 245.13 pg/ml) than controls (151.81 +/- 125.90 pg/ml) (p < 0.05). 5-HT was undetectable in saliva. Neither plasma 5-HT, nor SP levels differed between groups. BDNF and NGF concentrations correlated to levels of psychological distress (p < 0.0005). Conclusion The higher levels of salivary and plasma glutamate in patients with TMD-myalgia compared to controls strengthens its importance in the pathophysiology of TMD-myalgia. However, the lack of correlation to pain levels question its role as a putative biomarker. Patients with TMD-myalgia further had lower levels of salivary NGF and BDNF, but higher plasma BDNF. These results and their correlations to psychological distress warrant further investigations.
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26.
  • Jonsson, Pernilla, 1978, et al. (författare)
  • Holding on to the indispensable medication –A grounded theory on medication use from the perspective of persons with medication overuse headache
  • 2013
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 14:43, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Medication overuse headache (MOH) is a chronic headache disorder, caused by overuse of acute medication. To date, it remains unclear why some people overuse these medications. The aim of this qualitative study was to explore how individuals with MOH use medications and other strategies to manage headaches in their daily lives, and their thoughts about their own use of acute medication. Our intention was to develop a theoretical model about the development of MOH, from the perspective of those with MOH. Methods: Data collection and analysis were conducted according to grounded theory methodology. The participants were recruited via newspaper advertisements. Fourteen persons with MOH were interviewed in individual qualitative interviews. Results: The basic process leading to medication overuse was holding on to the indispensable medication. The acute medication was indispensable to the participants because they perceived it as the only thing that could prevent headaches from ruining their lives. The participants perceived headaches as something that threatened to ruin their lives. As a result, they went to great lengths trying to find ways to manage it. They tried numerous strategies. However, the only strategy actually perceived as effective was the use of acute medication and they eventually became resigned to the idea that it was the only effective aid. The acute medication thus became indispensable. Their general intention was to use as little medication as possible but they found themselves compelled to medicate frequently to cope with their headaches. They did not like to think about their medication use and sometimes avoided keeping track of the amount used. Conclusions: This qualitative study adds understanding to the process via which MOH develops from the perspective of those having MOH. Such knowledge may help bridge the gap between the perspectives of patients and health-care professionals.
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27.
  • Jonsson, Pernilla, 1978, et al. (författare)
  • Sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache
  • 2012
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 13:4, s. 281-290
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to analyse sociodemographic differences in medication use, health-care contacts and sickness absence among individuals with medication-overuse headache (MOH). A cross-sectional, population survey was conducted, in which 44,300 Swedes (a parts per thousand yen15 years old) were interviewed over telephone. In total, 799 individuals had MOH. Of these, 47 % ( = 370) only used over-the-counter medications. During the last year, 46 % ( = 343) had made a headache-related visit to their physician and 14 % ( = 102) had visited a neurologist. Among individuals aged < 30 years, the number of days/month with headache was greater than the number of days with medication use, whereas the opposite was true for those a parts per thousand yen30 years. Both the proportion using prophylactic medication and the proportion having consulted a neurologist were smaller among those who only had elementary school education than among those with higher education ( = 0.021 and = 0.046). Those with a lower level of education also had a higher number of days/month with headache and with medication use than those with a higher educational level ( = 0.011 and = 0.018). The MOH-sufferers have limited contacts with health-care and preventive measures thus need to include other actors as well. Particular efforts should be directed towards those with low educational levels, and more research on medication use in relation to age is required.
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28.
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29.
  • Krøll, Lotte Skytte, et al. (författare)
  • Level of physical activity, well-being, stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain
  • 2017
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of migraine with co-existing tension-type headache and neck pain is high in the general population. However, there is very little literature on the characteristics of these combined conditions. The aim of this study was to investigate a) the prevalence of migraine with co-existing tension-type headache and neck pain in a clinic-based sample, b) the level of physical activity, psychological well-being, perceived stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain compared to healthy controls, c) the perceived ability of persons with migraine and co-existing tension-type headache and neck pain to perform physical activity, and d) which among the three conditions (migraine, tension-type headache or neck pain) is rated as the most burdensome condition. Methods: The study was conducted at a tertiary referral specialised headache centre where questionnaires on physical activity, psychological well-being, perceived stress and self-rated health were completed by 148 persons with migraine and 100 healthy controls matched by sex and average age. Semi-structured interviews were conducted to assess characteristics of migraine, tension-type headache and neck pain. Results: Out of 148 persons with migraine, 100 (67%) suffered from co-existing tension-type headache and neck pain. Only 11% suffered from migraine only. Persons with migraine and co-existing tension-type headache and neck pain had lower level of physical activity and psychological well-being, higher level of perceived stress and poorer self-rated health compared to healthy controls. They reported reduced ability to perform physical activity owing to migraine (high degree), tension-type headache (moderate degree) and neck pain (low degree). The most burdensome condition was migraine, followed by tension-type headache and neck pain. Conclusions: Migraine with co-existing tension-type headache and neck pain was highly prevalent in a clinic-based sample. Persons with migraine and co-existing tension-type headache and neck pain may require more individually tailored interventions to increase the level of physical activity, and to improve psychological well-being, perceived stress and self-rated health.
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30.
  • Larsson, Bo, et al. (författare)
  • Headache prevalence and characteristics among adolescents in the general population : a comparison between retrospect questionnaire and prospective paper diary data
  • 2014
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 15, s. 80-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the present school-based study, a convenience sample of 237 adolescents in grade 6-9 and second year in high school (age 12-18 years) was recruited from a city and a smaller town. The aim of the study was to compare information on the prevalence and various characteristics of headaches not related to disease in a retrospect questionnaire and prospective daily recordings of headaches in a standard paper diary during a 3-week period. Methods: Besides headache severity, number of headache days, intensity levels and duration of headache episodes were estimated with both assessment methods. Most of the school children suffered from tension-type headaches and a smaller portion of migraine attacks. Results: The overall results showed that school children significantly (p < 0.001) overestimated headache intensity in questionnaires as compared to diary recordings, whereas they underestimated frequency (p < 0.001) and duration (p < 0.001) of headaches. While the correlations on headache severity, frequency and duration between retrospect information in questionnaires and prospective diary recordings were low, the agreement varied with levels of headache characteristics. Conclusions: Our findings concur well with results from a few similar community studies on headache complaints in school-aged children. We recommend that prospective recordings in diaries should be systematically used in clinical practice but also in epidemiological surveys to increase the validity and reliability in estimates of point prevalence of headache complaints in children and adolescents.
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31.
  • Larsson, Bo, et al. (författare)
  • Headache prevalence and characteristics among school children as assessed by prospective paper diary recordings
  • 2012
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 13:2, s. 129-136
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present school-based study, a convenience sample of 477 students in grades 6-9 and second year in high school from a city and a smaller town recorded daily occurrence and intensity of headaches in a standard paper diary during a 3-week period. Total headache activity (headache sum), number of headache days, intensity level and duration for weekly headaches were estimated. Approximately 85% of the adolescents had experienced headache of any intensity level during the 3-week recording period. On the average, they reported 2.5 headache days per week and a mean intensity level for headache episodes of 1.7. Our estimates for headache of any intensity level (1-5) occurring at least once a week was surprisingly high (73.8%). For the highest intensity level across the whole 3-week period, almost identical proportions of mild and moderate headaches were reported by students (22.3-22.5%), while about twice as many (40.7%) had experienced severe headaches. Girls consistently reported more headaches than boys, in particular of the moderate and severe intensity types. Students in the city also reported more frequent and intense headaches than those in the town. Peak headache activity was observed at noon and in the afternoon and in the days from the middle of the week until weekend. The use of prospective recordings in diaries will further advance our knowledge on the prevalence and characteristics of recurrent headaches among children and adolescents in community samples.
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32.
  • Link, Andrea, et al. (författare)
  • Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system.
  • 2008
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers.
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33.
  • Louca Jounger, Sofia, et al. (författare)
  • Increased levels of intramuscular cytokines in patients with jaw muscle pain
  • 2017
  • Ingår i: Journal of Headache and Pain. - : Springer. - 1129-2369 .- 1129-2377. ; 18:30
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to investigate cytokine levels in the masseter muscle, their response to experimental tooth-clenching and their relation to pain, fatigue and psychological distress in patients with temporomandibular disorders (TMD) myalgia. Methods: Forty women, 20 with TMD myalgia (Diagnostic Criteria for TMD) and 20 age-matched healthy controls participated. Intramuscular microdialysis was performed to sample masseter muscle cytokines. After 140 min (baseline), a 20-minute tooth-clenching task was performed (50% of maximal voluntary contraction force). Pain (Numeric rating scale 0-10) and fatigue (Borg's Ratings of Perceived Exertion 6-20) were assessed throughout microdialysis, while pressure-pain thresholds (PPT) were assessed before and after microdialysis. Perceived stress (PSS-10) and Trait Anxiety (STAI) were assessed before microdialysis. Results: The levels of IL-6, IL-7, IL-8 and IL-13 were higher in patients than controls (Mann Whitney U-test; P's < 0. 05) during the entire microdialysis. IL-6, IL-8 and IL-13 changed during microdialysis in both groups (Friedman; P's < 0.05), while IL-1 beta, IL-7 and GM-CSF changed only in patients (P's < 0.01). IL-6 and IL-8 increased in response to tooth-clenching in both groups (Wilcoxon test; P's < 0.05), while IL-7, IL-13 and TNF increased only in patients (P's < 0.05). Patients had higher pain and fatigue than controls before and after tooth-clenching (P < 0.001), and lower PPTs before and after microdialysis (P < 0.05). There were no correlations between cytokine levels, pain or fatigue. Also, there were no differences in stress or anxiety levels between groups. Conclusions: In conclusion, the masseter levels of IL-6, IL-7, IL-8 and IL-13 were elevated in patients with TMD myalgia and increased in response to tooth-clenching. Tooth-clenching increased jaw muscle pain and fatigue, but without correlations to cytokine levels. This implies that subclinical muscle inflammation may be involved in TMD myalgia pathophysiology, but that there is no direct cause-relation between inflammation and pain.
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34.
  • Louca, Sofia, et al. (författare)
  • Serotonin, glutamate and glycerol are released after the injection of hypertonic saline into human masseter muscles : a microdialysis study
  • 2014
  • Ingår i: Journal of Headache and Pain. - : Springer. - 1129-2369 .- 1129-2377. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic myalgia is associated with higher muscle levels of certain algesic biomarkers. The aim of this study was to investigate if hypertonic saline-induced jaw myalgia also leads to release of such biomarkers and if there were any sex differences in this respect. METHODS: Healthy participants, 15 men and 15 aged-matched women (25.7 ± 4.3 years) participated. Intramuscular microdialysis into masseter muscles was performed to sample serotonin (5-HT), glutamate, lactate, pyruvate, glucose and glycerol. After 2 hours 0.2 mL hypertonic saline (58.5 mg/mL) was injected into the masseter on one side and 0.2 mL isotonic saline (9 mg/mL) into the contralateral masseter close to the microdialysis catheter. Microdialysis continued for 1 hour after the injections. Pressure pain thresholds (PPT) and pain were assessed before and after injections. RESULTS: The median (IQR) peak pain intensity (0-100 visual analogue scale) after hypertonic saline was 52.5 (38.0) and after isotonic saline 7.5 (24.0) (p < 0.05). 5-HT, glutamate and glycerol increased after hypertonic saline injection (p < 0.05). Lactate, pyruvate and glucose showed no change. PPT after microdialysis was reduced on both sides (p < 0.05) but without side differences. Pain after hypertonic saline injection correlated positively to 5-HT (p < 0.05) and negatively to glycerol (p < 0.05). CONCLUSIONS: 5-HT, glutamate and glycerol increased after a painful hypertonic saline injection into the masseter muscle, but without sex differences. Since increased levels of 5-HT and glutamate have been reported in chronic myalgia, this strengthens the validity of the pain model. Glycerol warrants further investigations.
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35.
  • Lukács, Melinda, et al. (författare)
  • Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion.
  • 2015
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater induces inflammatory activation in the trigeminal ganglion.
  •  
36.
  • Lukács, M., et al. (författare)
  • KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1/2 and IL-1β in the rat trigeminal ganglion
  • 2016
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neurogenic inflammation has for decades been considered an important part of migraine pathophysiology. In the present study, we asked the question if administration of a novel kynurenic acid analogue (SZR72), precursor of an excitotoxin antagonist and anti-inflammatory substance, can modify the neurogenic inflammatory response in the trigeminal ganglion. Methods: Inflammation in the trigeminal ganglion was induced by local dural application of Complete Freunds Adjuvant (CFA). Levels of phosphorylated MAP kinase pERK1/2 and IL-1β expression in V1 region of the trigeminal ganglion were investigated using immunohistochemistry and Western blot. Findings: Pretreatment with one dose of SZR72 abolished the CFA-induced pERK1/2 and IL-1β activation in the trigeminal ganglion. No significant change was noted in case of repeated treatment with SZR72 as compared to a single dose. Conclusions: This is the first study that demonstrates that one dose of KYNA analog before application of CFA can give anti-inflammatory response in a model of trigeminal activation, opening a new line for further investigations regarding possible effects of KYNA derivates.
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37.
  • Lukács, M., et al. (författare)
  • Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis : attenuated by KYNA derivate (SZR72)
  • 2017
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Migraine is a debilitating neurological disorder where trigeminovascular activation plays a key role. We have previously reported that local application of Complete Freund’s Adjuvant (CFA) onto the dura mater caused activation in rat trigeminal ganglion (TG) which was abolished by a systemic administration of kynurenic acid (KYNA) derivate (SZR72). Here, we hypothesize that this activation may extend to the trigeminal complex in the brainstem and is attenuated by treatment with SZR72. Methods: Activation in the trigeminal nucleus caudalis (TNC) and the trigeminal tract (Sp5) was achieved by application of CFA onto the dural parietal surface. SZR72 was given intraperitoneally (i.p.), one dose prior CFA deposition and repeatedly daily for 7 days. Immunohistochemical studies were performed for mapping glutamate, c-fos, PACAP, substance P, IL-6, IL-1β and TNFα in the TNC/Sp5 and other regions of the brainstem and at the C1-C2 regions of the spinal cord. Results: We found that CFA increased c-fos and glutamate immunoreactivity in TNC and C1-C2 neurons. This effect was mitigated by SZR72. PACAP positive fibers were detected in the fasciculus cuneatus and gracilis. Substance P, TNFα, IL-6 and IL-1β immunopositivity were detected in fibers of Sp5 and neither of these molecules showed any change in immunoreactivity following CFA administration. Conclusion: This is the first study demonstrating that dural application of CFA increases the expression of c-fos and glutamate in TNC neurons. Treatment with the KYNA analogue prevented this expression.
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38.
  • Lundblad, Cornelia, et al. (författare)
  • Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.
  • 2015
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage.
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39.
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40.
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41.
  • Martelletti, Paolo, et al. (författare)
  • The changing faces of migraine
  • 2019
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 20:1
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
42.
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43.
  • Mignot, Coralie, et al. (författare)
  • Migraine with aura : less control over pain and fragrances?
  • 2023
  • Ingår i: Journal of Headache and Pain. - : BioMed Central (BMC). - 1129-2369 .- 1129-2377. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAccumulating data emphasizes the importance of olfaction in migraine pathophysiology. However, there are only a few studies evaluating how the migraine brain processes olfactory stimulation, and virtually no studies comparing patients with and without aura in this context.MethodsThis cross-sectional study recorded event-related potentials from 64 electrodes during a pure olfactory or pure trigeminal stimulus in females with episodic migraine with aura (n = 13) and without aura (n = 15), to characterize the central nervous processing of these intranasal stimuli. Patients were tested in interictal state only. Data were analyzed in the time domain and in the time-frequency domain. Source reconstruction analysis was also performed.ResultsPatients with aura had higher event-related potentials amplitudes for left-sided trigeminal and left-sided olfactory stimulations, and higher neural activity for right-sided trigeminal stimulation in brain areas related to trigeminal and visual processing. Following olfactory stimulations patients with aura displayed decreased neural activity in secondary olfactory structures compared to patients without aura. Oscillations in the low frequency bands (< 8 Hz) differed between patient groups.ConclusionsAltogether this may reflect hypersensitivity to nociceptive stimuli in patients with aura relative to patients without aura. Patients with aura have a bigger deficit in engaging secondary olfactory-related structures, possibly leading to distorted attention and judgements towards odors. The cerebral overlap between trigeminal nociception and olfaction might explain these deficits.
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44.
  • Mitsikostas, Dimos D., et al. (författare)
  • Refractory chronic cluster headache: a consensus statement on clinical definition from the European Headache Federation
  • 2014
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic cluster headache (CCH) often resists to prophylactic pharmaceutical treatments resulting in patients' life damage. In this rare but pragmatic situation escalation to invasive management is needed but framing criteria are lacking. We aimed to reach a consensus for refractory CCH definition for clinical and research use. The preparation of the final consensus followed three stages. Internal between authors, a larger between all European Headache Federation members and finally an international one among all investigators that have published clinical studies on cluster headache the last five years. Eighty-five investigators reached by email. Proposed criteria were in the format of the International Classification of Headache Disorders III-beta (description, criteria, notes, comments and references). Following this evaluation eight drafts were prepared before the final. Twenty-four (28.2%) international investigators commented during two rounds. Refractory CCH is described in the present consensus as a situation that fulfills the criteria of ICHD-3 beta for CCH with at least three severe attacks per week despite at least three consecutive trials of adequate preventive treatments. The condition is rare, but difficult to manage and invasive treatments may be needed. The consensus addresses five specific clinical and paraclinical diagnostic criteria followed by three notes and specific comments. Although refractory CCH may be not a separate identity these specific diagnostic criteria should help clinicians and investigators to improve patient's quality of life.
  •  
45.
  •  
46.
  • Ohlsson, Lena, et al. (författare)
  • Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries
  • 2018
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fremanezumab (TEV-48125) is a fully humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) that has shown positive results in the prevention of episodic migraine and chronic migraine. Previous preclinical studies have revealed CGRP antagonistic effects on intracranial arteries (ICA). The aim of the study was to evaluate the in vitro antagonistic effects of fremanezumab on human arteries. Methods: Arteries were removed in conjunction with neurosurgery (cerebral, CA, and middle meningeal artery, MMA, n = 7) or reconstructive abdominal surgery (abdominal artery, AA, n = 6). Ring segments of the vessels were mounted in a sensitive myograph, the functional responses of vasoactive intestinal peptide (VIP), substance P and CGRP in increasing concentrations (10- 10-10- 7 M) were studied using pre-contraction with 30 mM potassium chloride (KCl). The concentrations of fremanezumab or isotype control antibody (66.7 nM, 0.33 μM, 0.67 μM) were given 30 min prior to CGRP administration. Results: All included arteries responded with a strong stable contraction to the application of 30 mM KCl. During this pre-contraction, CGRP caused a concentration-dependent relaxation which differed slightly in maximum effect (Imax) between the types of arteries (ICA = 100%; AA 80%). Fremanezumab (66.7 nM) showed a shift in the IC50 value of CGRP, but no significant change in Imax. At higher doses there was also a reduction of Imax. For AA, the Imax decreased from 71% at 66.7 nM, to 4.5% with 0.33 μM of fremanezumab. Isotype control antibody did not modify the responses. There was no effect on concentration-dependent relaxation with VIP with 66.7 nM of fremanezumab or isotype control. Conclusion: CGRP relaxes pre-contracted human arteries by 80-100%, but with different IC50; the potency range was ICA < AA. The antagonistic effect and potency of fremanezumab was similar, suggesting that there are vasodilatory CGRP receptors present in all studied arteries and that the antibody may have effect in all studied vessels.
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47.
  •  
48.
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49.
  • Rubio-Beltrán, Eloisa, et al. (författare)
  • PACAP38 and PAC1 receptor blockade : a new target for headache?
  • 2018
  • Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 19:1
  • Forskningsöversikt (refereegranskat)abstract
    • Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) is a widely distributed neuropeptide involved in neuroprotection, neurodevelopment, nociception and inflammation. Moreover, PACAP38 is a potent inducer of migraine-like attacks, but the mechanism behind this has not been fully elucidated.Migraine is a neurovascular disorder, recognized as the second most disabling disease. Nevertheless, the antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor are the only prophylactic treatment developed specifically for migraine. These antibodies have displayed positive results in clinical trials, but are not effective for all patients; therefore, new pharmacological targets need to be identified.Due to the ability of PACAP38 to induce migraine-like attacks, its location in structures previously associated with migraine pathophysiology and the 100-fold selectivity for the PAC1 receptor when compared to VIP, new attention has been drawn to this pathway and its potential role as a novel target for migraine treatment. In accordance with this, antibodies against PACAP38 (ALD 1910) and PAC1 receptor (AMG 301) are being developed, with AMG 301 already in Phase II clinical trials. No results have been published so far, but in preclinical studies, AMG 301 has shown responses comparable to those observed with triptans. If these antibodies prove to be effective for the treatment of migraine, several considerations should be addressed, for instance, the potential side effects of long-term blockade of the PACAP (receptor) pathway. Moreover, it is important to investigate whether these antibodies will indeed represent a therapeutic advantage for the patients that do not respond the CGRP (receptor)-antibodies.In conclusion, the data presented in this review indicate that PACAP38 and PAC1 receptor blockade are promising antimigraine therapies, but results from clinical trials are needed in order to confirm their efficacy and side effect profile.
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50.
  • Shimada, Akiko, et al. (författare)
  • Muscle pain sensitivity after glutamate injection is not modified by systemic administration of monosodium glutamate
  • 2015
  • Ingår i: Journal of Headache and Pain. - : SPRINGER-VERLAG ITALIA SRL. - 1129-2369 .- 1129-2377. ; 16:68
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Monosodium glutamate (MSG) is often thought to be associated with headache and craniofacial pains like temporomandibular disorders. This randomized, double-blinded, placebo-controlled study was performed to investigate how ingestion of MSG affects muscle pain sensitivity before and after experimentally induced muscle pain. Methods: Sixteen healthy adult subjects participated in 2 sessions with at least 1-week interval between sessions. In each session, two injections of glutamate (Glu, 0.5 M, 0.2 ml) and two injections of saline (0.9 %, 0.2 ml) into the masseter and temporalis muscles, respectively, were undertaken, with a 15 min interval between each injection. Injections of saline were made contralateral to Glu injections and done in a randomized order. Participants drank 400 mL of soda mixed with either MSG (150 mg/kg) or NaCl (24 mg/kg, placebo) 30 min before the intramuscular injections. Pressure pain thresholds (PPT), autonomic parameters and pain intensity were assessed prior to (baseline) and 30 min after ingestion of soda, as well as 5 min and 10 min after the intramuscular injections and at the end of the session. Whole saliva samples were collected prior to and 30, 45, 60, and 75 min after the ingestion of soda. Results: MSG administration resulted in a significantly higher Glu level in saliva than administration of NaCl and was associated with a significant increase in systolic blood pressure. Injections of Glu were significantly more painful than injections of NaCl. However, ingestion of MSG did not change the intensity of Glu-evoked pain. Glu injections also significantly increased systolic and diastolic blood pressure, but without an additional effect of MSG ingestion. Glu injections into the masseter muscle significantly reduced the PPT. However, pre-injection MSG ingestion did not significantly alter this effect. Interestingly, PPT was significantly increased in the trapezius after MSG ingestion and intramuscular injection of Glu in the jaw muscles. Conclusion: The main finding in this study was that systemic intake of a substantial amount of MSG does not influence either pain intensity or pressure pain sensitivity in the masseter and temporalis muscles into which Glu injections were made.
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