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- 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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2. |
- 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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3. |
- Eliasson, JH, et al.
(author)
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The prevalence of hypnic headache in Iceland
- 2020
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 40:8, s. 863-865
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Journal article (peer-reviewed)abstract
- To determine the prevalence of hypnic headache. Background The exact prevalence of hypnic headache is unknown since there are no published population-based prevalence studies. Methods This study was a pilot for the SAGA cohort study, a population-based study on life stressors and various indices of health. Of 1398 invited adults, 921 (66%) participated; 402 men (average age 45.6 years, SD 13.2) and 519 women (52.6 years, SD 11.1). Subjects answered a headache questionnaire including a screening question for hypnic headache. “Do you have a headache that occurs only during sleep and causes wakening?”. Diagnosis of hypnic headache was made by clinical interview using ICHD-3 criteria. Results Among 921 participants, six screened positive for hypnic headache, of those two 0.22% (95% CI 0.06–0.79%) had probable hypnic headache and none had definite hypnic headache. Conclusion Confirming that hypnic headache is rare, these data suggest a 0.22% prevalence of probable hypnic headache.
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4. |
- Exposto, Fernando G., et al.
(author)
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Pain in the temple? Headache, muscle pain or both : A retrospective analysis
- 2021
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In: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 41:14, s. 1486-1491
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Journal article (peer-reviewed)abstract
- Aim Headache attributed to temporomandibular disorders and myalgia are two diagnoses included in the diagnostic criteria for temporomandibular disorders (DC/TMD). However, it is not clear if these two diagnoses are different clinical entities given their similar presentation and way in which they are diagnosed, when the myalgia is within the temporalis muscle. The purpose of this retrospective study was to assess the overlap between headache attributed to temporomandibular disorders and myalgia of the temporalis muscle. Methods The charts of 671 patients seeking treatment at the Section of Orofacial Pain and Jaw Function, Aarhus University, Denmark, between January 2015 and February 2020 were screened for a diagnosis of headache attributed to temporomandibular disorders, myalgia of the temporalis muscle, or both. Results A total of 89 patients fulfilled the DC/TMD criteria for either headache attributed to TMD, myalgia of the temporalis or both. Of these, two had a diagnosis of headache attributed to TMD, 16 of myalgia of the temporalis, and 71 were diagnosed with both. In 97.3% of the times that headache attributed to temporomandibular disorders was diagnosed, the patient was also diagnosed with myalgia of the temporalis. The Jaccard index was 0.8, indicating a substantial overlap between the two diagnoses. Finally, the overlap of pain location between the two diagnoses was substantial, with a Jaccard index of 0.9. Conclusions In the present study, headache attributed to temporomandibular disorders was almost exclusively diagnosed together with myalgia of the temporalis. Therefore, we propose that headache attributed to temporomandibular disorders and myalgia of the temporalis muscle have more clinical similarities than differences and as such could be considered one single clinical entity. Further studies will be needed to address the clinical consequences of this proposal.
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5. |
- Fourier, C, et al.
(author)
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The molecular clock gene cryptochrome 1 (CRY1) and its role in cluster headache
- 2021
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 41:13, s. 1374-1381
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Journal article (peer-reviewed)abstract
- Cluster headache is a severe primary headache disorder commonly featuring a strikingly distinct circadian attack pattern. Therefore, the circadian system has been suggested to play a crucial role in the pathophysiology of cluster headache. Cryptochromes are key components of the molecular clock generating circadian rhythms and have previously been shown to be associated with several psychiatric disorders, including seasonal affective disorder, bipolar disorder, and depression. Methods In this case-control study, we investigated the role of cryptochrome ( CRY) genes in cluster headache by screening 628 cluster headache patients and 681 controls from Sweden for four known genetic variants in the CRY1 (rs2287161 and rs8192440) and CRY2 (rs10838524 and rs1554338) genes. In addition, we analyzed CRY1 gene expression in primary fibroblast cell lines from eleven patients and ten controls. Results The exonic CRY1 variant rs8192440 was associated with cluster headache on allelic level ( p=0.02) and this association was even more pronounced in a subgroup of patients with reported diurnal rhythmicity of attacks ( p=0.002). We found a small significant difference in CRY1 gene expression between cluster headache patients and control individuals ( p=0.04), but we could not identify an effect of the associated variant rs8192440 on CRY1 expression. Conclusions We discovered a disease-associated variant in the CRY1 gene and slightly increased CRY1 gene expression in tissue from cluster headache patients, strengthening the hypothesis of circadian dysregulation in cluster headache. How this gene variant may contribute to the pathophysiology of the disease remains subject to further studies.
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6. |
- May, Arne, et al.
(author)
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Orofacial pain for clinicians : A review of constant and attack-like facial pain syndromes
- 2023
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In: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 43:8
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Journal article (peer-reviewed)abstract
- BACKGROUND: Primary headache syndromes such as migraine are among the most common neurological syndromes. Chronic facial pain syndromes of non-odontogenic cause are less well known to neurologists despite being highly disabling. Given the pain localization, these patients often consult dentists first who may conduct unnecessary dental interventions even if a dental cause is not identified. Once it becomes clear that dental modalities have no effect on the pain, patients may be referred to another dentist or orofacial pain specialist, and later to a neurologist. Unfortunately, neurologists are also often not familiar with chronic orofacial pain syndromes although they share the neural system, i.e., trigeminal nerve and central processing areas for headache disorders.CONCLUSION: In essence, three broad groups of orofacial pain patients are important for clinicians: (i) Attack-like orofacial pain conditions, which encompass neuralgias of the cranial nerves and less well-known facial variants of primary headache syndromes; (ii) persistent orofacial pain disorders, including neuropathic pain and persistent idiopathic facial/dentoalveolar pain; and (iii) other differential diagnostically relevant orofacial pain conditions encountered by clinicians such as painful temporomandibular disorders, bruxism, sinus pain, dental pain, and others which may interfere (trigger) and overlap with headache. It is rewarding to know and recognize the clinical picture of these facial pain syndromes, given that, just like for headache, an internationally accepted classification system has been published and many of these syndromes can be treated with medications generally used by neurologists for other pain syndromes.
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7. |
- Pisanu, Claudia, et al.
(author)
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Major depression subtypes are differentially associated with migraine subtype, prevalence and severity
- 2020
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:4, s. 347-356
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Migraine and major depressive disorder show a high rate of comorbidity, but little is known about the associations between the subtypes of major depressive disorder and migraine. In this cross-sectional study we aimed at investigating a) the lifetime associations between the atypical, melancholic, combined and unspecified subtype of major depressive disorder and migraine with and without aura and b) the associations between major depressive disorder and its subtypes and the severity of migraine.METHODS: A total of 446 subjects with migraine (migraine without aura: n = 294; migraine with aura: n = 152) and 2511 controls from the population-based CoLaus/PsyCoLaus study, Switzerland, were included. Associations between major depressive disorder subtypes and migraine characteristics were tested using binary logistic or linear regression.RESULTS: Melancholic, combined and unspecified major depressive disorder were associated with increased frequency of migraine with aura, whereas only melancholic major depressive disorder was associated with increased frequency of migraine without aura. Lifetime and unspecified major depressive disorder were associated with severe migraine intensity among subjects with migraine with aura but not migraine without aura, while combined major depressive disorder was associated with higher migraine frequency independently from migraine subtype.CONCLUSION: This study suggests that melancholic but not atypical major depressive disorder is associated with migraine and migraine subtypes. Future studies exploring pathophysiological mechanisms shared between melancholic depression and migraine are warranted.
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8. |
- Strang-Karlsson, S, et al.
(author)
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Migraine in children and adults born preterm: A nationwide register linkage study
- 2021
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 41:6, s. 677-689
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Journal article (peer-reviewed)abstract
- Being born preterm is related to adverse health effects later in life. We studied whether preterm birth predicts the risk of migraine. Methods In this nationwide register study, we linked data from six administrative registers for all 235,624 children live-born in Finland (January 1987 to September 1990) and recorded in the Finnish Medical Birth Register. n = 228,610 (97.0%) had adequate data and were included. Migraine served as primary outcome variable and was stringently defined as a diagnosis from specialised health care and/or ≥2 reimbursed purchases of triptans. We applied sex- and birth year-stratified Cox proportional hazard regression models to compute hazard ratios and confidence intervals (95% confidence intervals) for the association between preterm categories and migraine. The cohort was followed up until an average age of 25.1 years (range: 23.3–27.0). Results Among individuals born extremely preterm (23–27 completed weeks of gestation), the adjusted hazard ratios for migraine was 0.55 (0.25–1.24) when compared with the full-term reference group (39–41 weeks). The corresponding adjusted hazard ratios and 95% confidence intervals for the other preterm categories were: Very preterm (28–31 weeks); 0.95 (0.68–1.31), moderately preterm (32–33 weeks); 0.96 (0.73–1.27), late preterm (34–36 weeks); 1.01 (0.91–1.11), early term (37–38 weeks); 0.98 (0.93–1.03), and post term (42 weeks); 0.98 (0.89–1.08). Migraine was predicted by parental migraine, lower socioeconomic position, maternal hypertensive disorder and maternal smoking during pregnancy. Conclusion We found no evidence for a higher risk of migraine among individuals born preterm.
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9. |
- Sundholm, A, et al.
(author)
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A national Swedish case-control study investigating incidence and factors associated with idiopathic intracranial hypertension
- 2021
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 41:14, s. 1427-1436
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Journal article (peer-reviewed)abstract
- To study the incidence of idiopathic intracranial hypertension in Sweden and to explore whether previously proposed risk factors are associated with idiopathic intracranial hypertension by investigating the odds of exposure one year prior to diagnosis in patients compared to controls. Methods Using Swedish health care registers and validated diagnostic algorithms, idiopathic intracranial hypertension patients diagnosed between 2000–2016 were compared with randomly selected matched controls, five from the general population and five with obesity. Results We identified 902 idiopathic intracranial hypertension patients and 4510 matched individuals in each control group. Mean incidence among inhabitants ≥18 years of age was 0.71 per 100,000; rising from 0.53 in 2000–2005 to 0.95 in 2012–2016. There were increased odds for idiopathic intracranial hypertension patients compared to general population for exposure to: kidney failure (odds ratio =13.2 (4.1–42.0)), arterial hypertension (odds ratio =17.5 (10.5–29.3)), systemic lupus erythematosus (odds ratio =13.8 (4.3–44.7)), tetracyclines, sulphonamides, lithium, and corticosteroids. In obese controls, odds ratios were also significantly increased for these exposures. Hormonal contraceptive use and exposure to pregnancy did not appear to be associated factors for idiopathic intracranial hypertension development. Conclusions The incidence of idiopathic intracranial hypertension in Sweden is lower relative to reports from other countries but is on the rise. This case-control study confirms several previously reported risk factors associated with idiopathic intracranial hypertension.
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10. |
- Sundholm, A, et al.
(author)
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Infectious and inflammatory disorders might increase the risk of developing idiopathic intracranial hypertension - a national case-control study
- 2020
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In: Cephalalgia : an international journal of headache. - : SAGE Publications. - 1468-2982. ; 40:10, s. 1084-1094
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Journal article (peer-reviewed)abstract
- To investigate whether conditions causing inflammatory activation are associated with increased risk of idiopathic intracranial hypertension. Methods All newly diagnosed idiopathic intracranial hypertension patients (cases) in Sweden between 2000–2016 were identified using pre-determined algorithms (n = 902) and matched with five controls from the general population and five individuals with an obesity diagnosis (n = 4510) for age, sex, region, and vital status. National health registers provided information on infections, inflammatory disorders and dispensed medications. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Results Compared to general population controls, the cases had fourfold increased odds of having an infection (odds ratio = 4.3, 95% confidence interval 3.3–5.6), and threefold increased odds of an inflammatory disorder the year prior to idiopathic intracranial hypertension diagnosis (odds ratio = 3.2, 95% confidence interval 2.4–4.3). Organ specific analyses showed that odds were increased for the study diseases in the respiratory organ, kidney organ and gastrointestinal tract, but not for female genital infections. Similar results were found when comparing idiopathic intracranial hypertension with obese controls though the odds ratios were of lower magnitude. Sub-analyses on exposure to anti-infectious and anti-inflammatory drugs confirmed the increased odds ratios for idiopathic intracranial hypertension patients. Conclusions These findings suggest that major inflammatory activation may be a risk factor in idiopathic intracranial hypertension development.
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11. |
- Taneja, Pankaj, et al.
(author)
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Reliability of orofacial quantitative sensory testing for pleasantness and unpleasantness
- 2020
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In: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 40:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Quantitative sensory testing protocols for perceptions of pleasantness and unpleasantness based on the German Research Network on Neuropathic Pain protocol were recently introduced. However, there are no reliability studies yet published.AIM: To evaluate the intra-examiner (test-retest) and inter-examiner reliability for orofacial pleasantness and unpleasantness quantitative sensory testing protocols.METHODS: Sixteen healthy participants from Aarhus University (11 women and five men, mean age 24, range 21-26 years) contributed. Two examiners were trained in performing the entire quantitative sensory testing protocols for pleasantness and unpleasantness, which included the additional dynamic tactile stimulation test using a goat-hair brush. Each participant underwent examination of both protocols by each examiner (inter-examiner reliability) on day 1. They returned at least 8 days following the testing to be re-examined by one examiner (intra-examiner reliability). All testing was performed on the skin of the right mandibular mental region. The intraclass correlation (ICC) was used to determine reliability.RESULTS: For the protocol investigating pleasantness, the majority of parameters had good to excellent intra-examiner (11/14: Intraclass correlation 0.67-0.87) and inter-examiner (13/14: Intraclass correlation 0.62-0.96) reliabilities. Similarly, the protocol investigating unpleasantness had good to excellent intra-examiner (intraclass correlation 0.63-0.99) and inter-examiner (intraclass correlation 0.65-0.98) reliabilities for most (13/15) of the parameters.CONCLUSION:Intra and inter-examiner reliabilities in the majority of quantitative sensory testing parameters (apart from the summation ratio) investigating pleasantness and unpleasantness are acceptable when assessing somatosensory function of the orofacial region.Trial registration: NA.
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- Warfvinge, Karin, et al.
(author)
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Cellular distribution of PACAP-38 and PACAP receptors in the rat brain : Relation to migraine activated regions
- 2020
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In: Cephalalgia. - : SAGE Publications. - 0333-1024 .- 1468-2982. ; 40:6, s. 527-542
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Journal article (peer-reviewed)abstract
- Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) occurs as either a 27- or 38-amino acid neuropeptide and belongs to the vasoactive intestinal polypeptide/glucagon/secretin family of peptides. PACAP and vasoactive intestinal polypeptide have a 68% homology of their amino acid sequences and share three B-type G-protein coupled receptors: VPAC1, VPAC2 and PAC1 receptors. Methods/results: The distribution of PACAP-38 and its receptors in the brain is only partly described in the literature. Here, we have performed a study to provide the more general picture of this system in rat brain in order to understand a putative role in primary headaches and partly in relation to the calcitonin gene-related peptide system. We observed a rich expression of PACAP-38 and PAC1 receptor immunoreactivity in many regions throughout the cerebrum, cerebellum and brainstem. The expression pattern points to multiple functions, not least associated with pain and reactions to pain. The expression of VPAC1 and VPAC2 receptor immunoreactivity was very sparse. In several regions such as the cerebral cortex, trigeminal nucleus caudalis, hypothalamus and pons there was a close relation to calcitonin gene-related peptide expression. Conclusion: The findings suggest that the rich supply of PACAP-38 and PAC1 receptors is associated with basic functional responses in the central nervous system (CNS), and there are important close anatomical relations with calcitonin gene-related peptide in CNS regions associated with migraine pathophysiology.
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13. |
- Yang, Shuting, et al.
(author)
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Mechanical sensitivity changes in pericranial muscles after local anesthesia and experimentally induced pain in the temporalis tendon : Implications for headache and facial pain
- 2022
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In: Cephalalgia. - : Sage Publications. - 0333-1024 .- 1468-2982. ; 42:11-12, s. 1127-1137
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To assess changes in mechanical sensitivity of the pericranial muscles in healthy individuals after a local anesthetic block of the temporalis tendon. In addition, to assess, if experimentally induced temporalis tendon pain, can lead to an increase in mechanical sensitivity of the pericranial muscles and reports of headache.METHODS: 40 healthy participants were recruited for this randomized, double-blinded, controlled experiment, and were randomly injected with mepivacaine and isotonic saline into the dominant-side temporalis tendon in two different sessions, and either nerve growth factor (n = 20) or isotonic saline (n = 20) in a third session. Mechanical sensitivity was assessed in the temporalis, masseter, and trapezius muscles as well as in the temporalis tendon, on the dominant side, before and 10 minutes after each injection, and in a fourth session two days after the third session. Pain drawings and headache diaries were kept for 30 days after the final session to register any developing pain or headache.RESULTS: Mepivacaine injection into the temporalis tendon caused a significant decrease in mechanical sensitivity in the temporal tendon (-54.5%) and the masseter (-15.4%) muscle (P < 0.05) but not the temporalis (-12.1%) and trapezius muscles (-12.7%) (P > 0.05). Nerve growth factor injection into the temporalis tendon caused a significant increase in mechanical sensitivity in the tendon (+15.4%) and masseter muscle (+14.4%) (P < 0.05) but not the temporalis (+2.8%) or trapezius muscles (+3.1%) (P > 0.05). A significant increase was found for headache frequency in the first seven days (P < 0.05) after nerve growth factor injection compared to after isotonic saline injection, but not intensity (P > 0.05).CONCLUSION: These findings suggest that the therapeutic effect of temporalis tendon anesthetic injections on facial pain and headaches are most likely not only due to a direct effect of the local anesthetic on the temporalis tendon but rather to a more generalized block of the nerves in the area. In addition, the temporal tendon may contribute to the pathophysiological processes of headache.
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14. |
- Ashina, Messoud, et al.
(author)
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Real-world effectiveness of fremanezumab for the preventive treatment of migraine : Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study
- 2023
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In: Cephalalgia. - 0333-1024. ; 43:11
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Journal article (peer-reviewed)abstract
- Background: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. Methods: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1–12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1–12. Safety was assessed through adverse events reported. Results: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1–12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. Conclusion: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries. Trial registration: encepp.eu: EUPAS35111.
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