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Migraine is a multifaceted brain disorder where multisensory disturbances are associated with headache. Yet sensory symptoms are conventionally justified by dysfunctions confined to the cerebral cortex, a perspective through the complex interplay of thalamocortical network would provide the entire picture, more pertinent to the central sensory processing. It is important to consider thalamus as a hub that integrates multiple domains via extensive connections among anatomically and functionally separate cortical areas. Accordingly, cortical spreading depression (CSD), implicated in migraine pathophysiology can be seen as a tool to disconnect thalamocortical network by functionally eliminating cerebral cortex. Hence, including thalamic reticular nucleus and higher order thalamic nuclei, which conveys the information transthalamically among visual, somatosensory, language and motor cortical areas, would greatly improve our current understanding of migraine.Key words:Migraine, headache, sensory discrimination, thalamocortical network, sensory integration, CSD

Tüm dünyanın koronavirus pandemisi ile savaştığı bu günlerde COVID-19 hastalığının insanlar üzerindeki nörolojik bulguları gün geçtikçe artan oranda saptanmaktadır. Bazı solunum yolu virüslerinin nöroinvazyon ile sinir sistemi tutulumu yapıp erken ya da geç dönemde bulgu verdiği bilmektedir. Baş ağrısı da santral sinir sistemini tutan hastalıklar içinde kimi zaman alarm semptom olarak değerlendirilmekte ve ağrının karakteri ve eşlikçi bulguları tanıda yol gösterici olmaktadır. Burada bilgi birikimlerimizin tespit edilen vakalarla artmakta olduğu dönemde COVID-19 ve baş ağrısı sıklığı ve ilişkisi gözden geçirilmiştir. Nowadays, when the whole world fights coronavirus pandemics, the neurological findings of this virus, which we know as COVID-19, are increasing day by day. We know that some respiratory viruses cause nervous system involvement with neuroinvasion and present in early or late periods. Headache is sometimes considered as an alarm symptom among diseases involving the central nervous system, and the character and accompanying findings of the pain are guiding in diagnosis. Here, the frequency and relationship between COVID-19 and headache was reviewed in the period when our knowledge was increasing with the cases detected.

Background Headache is the most common COVID-19-related neurological symptom. We aimed to reveal diagnostic clues of headache for COVID-19 infection and to investigate the course of primary headaches during the pandemic. Methods We developed a detailed web-based questionnaire screening the characteristics and course of headaches besides clinical COVID-19 features. The participants were grouped according to being diagnosed with COVID-19 infection or not, and having previous or new-onset headaches. The COVID-19 related headache features and their associations with other clinical features were investigated. A binary logistic regression model was performed to differentiate the characteristics of headache related to COVID-19. Findings A total of 3458 participants (2341 females;67.7%, 1495 healthcare workers;43.2%) with a mean age of 43.21 ± 11.2 years contributed to the survey. Among them, 262 participants had COVID-19 diagnosis and 126 (48.1%) were male. The rate of males in the group without COVID-19 was 31% (991 out of 3196 participants) showing significant gender difference between groups (p p p p = 0.04 for long duration and p Interpretation Bilateral, long-lasting headaches, resistance to analgesics and having male gender were more frequent in people with COVID-19 in conjunction with anosmia/ageusia and gastrointestinal complaints. These features may be helpful for diagnosing the headache related to COVID-19 during the pandemic.

Rationale There are controversial reports on the effects of gabapentin in respect to psychotic symptoms. Prepulse inhibition of the acoustic startle response is an operational measure of sensorimotor gating. In laboratory rodents, deficits in sensorimotor gating are used to model behavioral endophenotypes of schizophrenia. Sleep deprivation disrupts prepulse inhibition and can be used as a psychosis model to evaluate effects of gabapentin. Objectives This study aimed to investigate behavioral effects of gabapentin in both naive and sleep-deprived rats. Methods Sleep deprivation was induced in male Wistar rats by using the modified multiple platform technique in a water tank for 72 h. The effect of water tank itself was studied in a sham group. The effects of oral acute and subchronic (4.5 days) gabapentin doses (25, 100,or 200 mg/kg/day) on sensorimotor gating and locomotor activity was evaluated by prepulse inhibition test and locomotor activity test, respectively. Plasma gabapentin levels of some groups and body weights of all groups were also assessed. Results Sleep deprivation disrupted prepulse inhibition, increased locomotor activity, reduced gabapentin plasma levels,and body weights. Some gabapentin doses disrupted sensorimotor gating irrespective of sleep condition. Some gabapentin doses increased locomotor activity in non-sleep-deprived rats and decreased locomotor activity in sleep-deprived rats. On the contrary, gabapentin did not normalize sleep deprivation-induced disruption in sensorimotor gating. Conclusions Sleep deprivation via modified multiple platform technique could be used as an animal model for psychosis. Gabapentin may have dose-and duration-dependent effects on sensorimotor gating and locomotor activity.

A well-balanced intracellular iron trafficking in glial cells plays a role in homeostatic processes. Elevated intracellular iron triggers oxidative stress and cell damage in many neurological disorders, including migraine. This study aimed to investigate the effects of glyceryl trinitrate (GTN), on cellular iron homeostasis, matrixmetalloproteinase (MMP)-9, and calcitonin gene related peptide (CGRP) receptor (CRLR/CGRPR1) production in microglia, astrocyte, and meningeal cell cultures. Primary glial and meningeal cells in culture were exposed to GTN for 24 h. Messenger RNA expression was assessed using qPCR. Iron accumulation was visualized via modified Perl’s histochemistry. MMP-9 levels in cell culture supernatants were measured using ELISA. Ferritin and CRLR/CGRPR1 proteins were visualized via immunofluorescence staining. Nitric oxide production increased significantly with GTN in meningeal and glial cells. GTN significantly increased the expression of the storage protein ferritin for all three cell types, but ferritin-L for meningeal cells and microglia. Iron trafficking associated with the efflux protein ferroportin and influx protein divalent metal transporter (DMT)1 was affected differently in all three cell types. MMP-9 expression was increased in astrocytes. GTN stimulation increased both CRLR/CGRPR1 expression, and immunostaining was apparent in microglia and meningeal cells. This study showed for the first time that GTN modulates intracellular iron trafficking regulated by storage and transport proteins expressed in meningeal cells and glia. CRLR/CGRPR1 expression might be related to altered iron homeostasis and they both may stimulate nociceptive pathways activated in migraine. These molecules expressed differently in glial and meningeal cells in response to GTN may bring not only new targets forward in treatment but also prevention in migraine.

BackgroundHeadache is the most common COVID-19-related neurological symptom. But, diagnostic clues of headache for COVID-19 infection are not well known. MethodsWe developed a detailed web-based questionnaire screening the characteristics and course of headaches besides clinical COVID-19 features. The participants were grouped according to being diagnosed with COVID-19 infection or not, and having previous or new-onset headaches. The COVID-19 related headache features and their associations with other clinical features were investigated. A binary logistic regression model was performed to differentiate the characteristics of headache related to COVID-19. Findings 3458 participants (2341 females;67.7%, 1495 healthcare workers;43.2%) with a mean age of 43.21±11.2 years experiencing headache during pandemic contributed to the survey. Among them, 262 participants had COVID-19 and 126(48.1%) were male. The rate of males in the group without COVID-19 was 31% (991 out of 3196 participants) showing significant gender difference between groups (p

Headache was reported in up to one-third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID-19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID-19 illness. Headache features in 13 PCR-confirmed COVID-19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID-19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine-like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patients were not suffering from primary headaches. It was concluded that headache could be an isolated symptom of COVID-19, which might possibly be ignored in asymptomatic patients. Headaches associated with COVID-19 included features resembling migraine and/or atypical symptoms including anosmia and diarrhea.

Tümdünyanın koronavirus pandemisi ile savaştığı bu günlerde COVID-19 hastalığınıninsanlar üzerindeki nörolojik bulguları gün geçtikçe artan orandasaptanmaktadır. Bazı solunum yolu virüslerinin nöroinvazyon ile sinir sistemitutulumu yapıp erken ya da geç dönemde bulgu verdiği bilmektedir. Baş ağrısı dasantral sinir sistemini tutan hastalıklar içinde kimi zaman alarm semptomolarak değerlendirilmekte ve ağrının karakteri ve eşlikçi bulguları tanıda yolgösterici olmaktadır. Burada bilgi birikimlerimizin tespit edilen vakalarlaartmakta olduğu dönemde COVID-19 ve baş ağrısı sıklığı ve ilişkisi gözdengeçirilmiştir

ÖZETTüm dünyanın koronavirus pandemisi ile savaştığıbu günlerde COVID-19 hastalığınıninsanlar üzerindekinörolojik bulgularıgün geçtikçe artan oranda saptanmaktadır. Bazısolunum yolu virüsleri- nin nöroinvazyonile sinir sistemitutulumu yapıp erken ya da geç dönemde bulgu verdiğibilmektedir. Başağrısıda santral sinir sisteminitutan hastalıklariçinde kimizaman alarm semptom olarak değer- lendirilmekte ve ağrının karakterive eşlikçibulgularıtanıda yol göstericiolmaktadır. Burada bilgibiri- kimlerimizin tespit edilen vakalarla artmakta olduğu dönemde COVID-19 ve başağrısısıklığıveilişkisigözden geçirilmiştir.Anahtar Kelimeler:Başağrısı; COVID-19; ACE2

After the emergence of a novel coronavirus named SARS-CoV-2, coronavirus disease 2019 (COVID-19) was initially characterized by fever, sore throat, cough, and dyspnea, mainly manifestations of respiratory system. However, other manifestations such as headache, abdominal pain, diarrhea, loss of taste and smell were added to the clinical spectrum, during the course of the COVID-19 pandemic. The reports on the neurological findings are increasing rapidly and headache seems to be the leader on the symptom list. Headache was reported in 11%-34% of the hospitalized COVID-19 patients, but clinical features of these headaches were totally missing in available publications. According to our initial experience, significant features of headache presentation in the symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were sudden to gradual onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19. Symptomatic COVID-19 patients, around 6%-10%, also reported headache as a presenting symptom. The possible pathophysiological mechanisms of headache include activation of peripheral trigeminal nerve endings by the SARS-CoV-2 directly or through the vasculopathy and/or increased circulating pro-inflammatory cytokines and hypoxia. We concluded that as a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny.

Background and objective The present study aimed to investigate the effects of selective calcitonin gene related peptide (CGRP) receptor antagonist (MK-8825) on cortical spreading depression (CSD) induced pain behavior and anxiety in freely-moving rats, and neuronal activation in the correlated anatomical regions. Methods CSD was induced while keeping all meningeal layers and BBB intact and MK-8825 was administered in two different doses. Regional cerebral blood flow (rCBF), arterial pressure and DC shift were recorded. Behavioral studies were conducted in freely-moving rats. Spontaneous behavior, mechanical allodynia, ultrasonic vocalization, and anxiety were evaluated. Immunohistochemistry of c-fos, CGRP, calcitonin receptor like-receptor (CLR) and receptor activity modifying protein 1 (RAMP1) were studied. Results MK-8825 did not block DC shifts in the cerebral cortex and accompanied hemodynamic response. CSD significantly induced freezing and grooming behavior in freely-moving rats. MK-8825 reversed increased episodes of freezing, grooming, wet dog shake and head shake behavior. MK-8825 increased CSD-induced reductions in von Frey thresholds, but did not change elevated plus maze results. MK-8825 blocked c-fos induction by CSD in the brainstem trigeminal nucleus caudalis (TNC) and reticular nucleus of thalamus (TRN) but not in the amygdala. Immunofluorescence analysis showed no co-localization of CGRP, CLR or RAMP1 with c-fos positive cells. Conclusion CGRP receptor antagonist MK-8825 dose dependently attenuated CSD-induced trigeminal nerve mediated pain response without altering CSD waves and accompanied rCBF response. While blocking TNC activation, MK-8825 did not exert any effect on amygdala and anxiety behavior. CGRP receptor antagonists may also modulate thalamo-cortical gating.

To clarify the causal relationship between migraine and atopic disorders in children and adolescents.Migraine headache and atopic disorders including asthma are both common functional syndromes of childhood in which nature of the relationship is still debated. Attacks may induce in both disorders upon exposure to potential triggers in genetically susceptible individuals. Clinical phenotype manifests by temporary dysfunction of target tissue mediated by inflammation triggered by specific agents. Clinical features also change after puberty because of the partial effect of female sex hormones on the process. Appropriate definition of the syndrome and differentiating from other disorders are necessary not only for correct diagnosis, but also for planning of management strategies in children. Allergic rhinosinusitis needs to be differentiated from migraine even in experienced clinics. Questioning the presence of cranial autonomic symptoms is important clue in the differential diagnosis. Atopic disorder screening is particularly required in the diagnosis of migraine in childhood and adolescents. The link between both disorders of childhood seems to be far from a coincidence and some common inflammatory mechanisms are shared.On the basis of clinical features, laboratory findings and some practical clues in children, accurate diagnosis of migraine and atopic disorders are very critical for physicians, pediatricians and algologists.

bstractObjective.It has been shown that patients with migraine have endothelial dysfunction. Migraine patients with aura, especially, have more clinical manifestations of autonomic nervous system dysfunction. We aimed to evaluate the endothelial and autonomic functions in migraine patients during both migraine headache attack and headache-free periods.Design.This was a cross-sectional, randomized study.Subjects and Methods.A total of 130 participants (67 male and 63 female patients, minimum age1⁄419 years, maximum age1⁄471 years, mean age1⁄438.8612.2 years) were enrolled into the study. For the statistical evaluation of data, we classified the participants of the study as fol- lows: group 1: headache (þ) aura (þ); group 2: headache (þ) aura (􏰀); group 3: headache (􏰀) aura (þ); group 4: head- ache (􏰀) aura (􏰀). Noninvasive evaluation of endothelial function was performed by flow-mediated dilation (FMD) and pulse wave analysis methods. Heart rate variability measurements were used for noninvasive evaluation of au- tonomic functions.Results.Group 1 had a higher FMD ratio than the control group, group 3, or group 4 (P0.001,P0.001, andP1⁄40.003, respectively). Group 4 had lower FMD ratio levels than the other migraine groups and or the control group (P0.001). Group 3 had the highest high-frequency (HF) power levels among all migraine groups (P<0.001). Group 2 had higher low-frequency/HF ratio values than other migraineurs (P<0.001).Conclusions.We concluded that endothelial dysfunction and headache are closely related. Additionally, higher parasympathetic to- nus might be associated with the presence of aura.Key Words:Migraine Disorders; Endothelium; Autonomic Nervous System Diseases

Additional file 1: Supplementary Table. Logistic regression analysis model to differentiate patients with COVID-19 from those without COVID-19 based on headache characteristics.

Introduction Interventions performed in the early period of life are associated with cognitive and behavioral changes in adulthood. The effects of interventions such as exposure to an early stressful life event or environmental enrichment on cognitive and behavioral development are studied. The aim of this study is to develop a new intervention method, to investigate the effects of early interventions on social interaction, memory anxiety levels and NR2B levels in prefrontal and hippocampus in adulthood. The hypothesis of the study is that exposure to the ambivalent mother will affect the behavioral performance of rats at least as much as one hour apart from the mother in the adult period and cause changes in the prefrontal cortex and hippocampus in the NR2B levels. Method In the study, the Wistar rats were divided into four groups as control group (12), group that remained 15 minutes apart from mother (Mild Stress) (12), group that remained 60 minutes apart from mother (Severe Stress) (14) and ambivalent mother group (13). In adulthood, the social interaction test, elevated plus maze and new object recognition test performances of rats were evaluated. ELISA method was used to evaluate the effect of interventions on the prefrontal cortex and hippocampus NMDA R2B levels. Results The important findings of the study were that in the new object recognition test, separation from the mother did not affect the recognition memory regardless of gender, while the short-term recognition memory of the females of the ambivalent mothers' group was better than the females in the other groups and the long-term memory performance of the mild stress groups men was better than the man in the other groups. In addition, in the social interaction test, the males of the ambivalent group and the mild stress group showed more aggressive behavior. It was determined that the prefrontal cortex NR2B level was higher in the mild stress and ambivalent mother group compared to the severe stress group, and NR2B level was increased in all intervention groups compared to the control group. Conclusion In contrast to the hypothesis, the results of this study support that the ambivalent mother's group rats are not more adversely affected than the severe group rats and that the model created may be an environmental enrichment model rather than an early stressful life event exposure.

Görsel zamansal ayrım (GZA), santral bir hedef noktası varlığında, periferik sunulan bir görsel uyaranın hareket, kontrast, konum, kontur gibi dikkat çeken özelliklerinin hızla tanımlanarak uyarana tepki verebilme yeteneğidir. GZA teorik olarak; retina, süperior kollikul, talamus, bazal gangliya devrelerinin yapısal bütünlüğü ve doğru entegrasyonu ile ilişkilidir.Çalışmamızda, ICHD-3 tanı kriterlerine uyan 15 aurasız migren ve 15 baş ağrısı olmayan gönüllü dahil edilmiştir. Migren hastaları atak ve interiktal dönemde olmak üzere 2 kere incelenerek, sağ görme alanı ve sol görme alanı için GZA değerleri ölçülmüştür. Migren hastalarında, atak sırasında atağın olduğu hemisfer, en sık atak tarafı, atak sıklığı, hastalık süresi, atak sırasında vizuel analog skala (VAS) skoru, fonofobi, fotofobi, fiziksel aktivite ile baş ağrısında şiddetlenmenin varlığı, bulantı, kusma ve allodini kaydedilmiştir. Çalışmamızda, migren hastalarında atak sırasında ve interiktal dönemde, GZA eşik değerlerini ikili LED ışıklarının 5 milisaniye (ms) asendan ve desendan intervallerle yanıp söndüğü bir sistemle ölçerek zamansal ayrım eşikleri belirlenmiştir.Çalışmada 15 migren hastasının interiktal ve iktal dönemdeki GZA eşik değerleri hem migren fazları içinde hem de kontroller ile kıyaslandığında, migren hastalarında her fazda kontrollere kıyasla GZA eşik değerlerinde belirgin artış gösterdiği bulundu. Ayrıca bu GZA eşik farkı iktal fazdaki migren hastalarında interiktal döneme göre belirgin bir artış olduğu gösterilmiştir. Çalışmamızda ayrıca VAS skorlarında artış, aylık atak sıklığında artış ve hastalarda iktal dönemde kusma görülmesinin GZA eşik değerlerini arttırdığı gösterilmiştir. GZA için nöroanatomik lokalizasyonlar dikkate alındığında migren hastalarında her dönem için beyin sapı,67bazal ganglion, talamik döngüler içinde duyusal modülasyonla ilgili defektif bir sürecin olduğunu göstermesi bakımından önem taşımaktadır.Bu çalışma, migren hastalarında GZA ile ilgili ilk çalışmadır. Bu çalışma migren atak ve interiktal dönemde GZA eşik değerlerinin kontrollere kıyasla belirgin uzama olmasının gösterilmesi açısından önem taşımaktadır. GZA çalışmasına beyin sapı uyarılmış potansiyelleri gibi elektrofizyolojik testlerin, fonksiyonel görüntüleme çalışmalarının eklenmesi, migrende beyin sapı, subkortikal döngüler üzerindeki inhibisyonu belirlemeye yönelik in vitro hayvan çalışmaları yapılması GZA bozukluğunun nerden kaynaklandığını ve patofizyolojisini anlamak açısından faydalı olacaktır. Visual temporal discrimination (VTD) is ability to discriminate and react to peripheral stimulus’s movement, contrast, location and contours etc. with control surface zero. VTD theoretically related with structural integrity and accurate integration of retina, superior colliculus, thalamus and basal ganglion network.15 patients diagnosed with migraine without aura according to ICHD-3 criteria and 15 volunteers who do not have headache were included in research. Migraine patients were examined twice during attack period and interictal period. VTD treshold values was determined both right and left visual field. In our research VTD treshold values determined in migraine patient during attack and interictal period with system that dual flashing lights with 5 millisecond (msc) ascending and descending intervals. Headache side during attack, most frequent headache side, headache frequency, duration off illness, visual analog scale (VAS) score during attack, photophobia, phonophobia, aggravation with phsyical activity, noisea, vomitting and allodynia was recorded.In our research VTD treshold values of migraine patients compairing with healthy volunteers in both attack and interictal period and found that treshold values of migraine patients’ were significantly higher than healthy volunterrs’ both attack and interctal period. Additionally VTD treshold values of migraine patients’ were much more higher in attack period. Additionally higher VAS score, higher attack frequencyand ıctal vomiting related with higher VTD treshold. According to neuroanatomic pathway of VTD, there is defective pathway about sensory modulation in brain stem, basal ganglion, thalamic pathway in imgraine patients. This research is important to show that pathway.This reseach is the first study about VTD in migraine patient. It is important to show that migraine patients’ VTD threshold higher than control group in both attack and interictal period. Additionally brain stem evoked potentials, functional imaging studies and in vitro animal studies will important to show where the neuroanatomical pathway effected and to understand the pathophysiology.

WOS:000583303300001 PubMed ID: 33124044 The coronavirus disease 2019 (COVID-19) pandemic has rapidly transformed the whole world and forced us to look through comorbid diseases and risk factors from a different perspective. COVID-19 shows some inherent risk factors like cardiovascular comorbidities independent from age, gender, and geographic location. One of the most peculiar features of the COVID-19 pandemic is that severe acute respiratory syndrome coronavirus 2 respiratory infections disproportionately impact patients with hypertension, diabetes, and other cardiovascular comorbidities rather than those with allergic respiratory diseases and immune-compromised conditions. Migraine is a complex neuro-vasculo-inflammatory disorder that is also packed frequently with certain medical conditions including vascular disorders, hypertension, allergic diseases such as asthma and systemic inflammatory disorders. Accordingly, 2 different questions arise during the pandemic: (1) Do share comorbidities of cardiovascular diseases and hypertension increase the risk of symptomatic COVID-19 for migraine patients? (2) Do comorbid allergic and atopic diseases, including asthma act as opposite influencers alongside with female gender? This paper focuses on the co-existence of comorbidities of COVID-19, in comparison with migraine, based on a wide clinical dataset and available reports. Discussed mechanisms include potential strategic roles of angiotensin-converting enzyme 2, angiotensin-II, and nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 inflammasome, playing remarkable parts in the pathogenesis of COVID-19 and migraine. There are also some clues about the importance of endothelial and pericyte dysfunction and neuroinflammation in COVID-19 infection, related to complications and survival of the patients. The large epidemiological studies as well as basic research, focusing on migraine patients with COVID-19 will clarify these vital questions during the upcoming periods. Turkish Academy of Sciences (TUBA)Turkish Academy of Sciences; Gazi UniversityGazi University; Istanbul UniversityIstanbul University The authors would like to thank Dr. Didem Derici Yildirim for re-analizing the data and producing Figure 1. The study partially supported by Turkish Academy of Sciences (TUBA), and Gazi University and Istanbul University Research Projects.

Background and Objective Migraine attacks disrupt sensory information processing and may also disturb sensorimotor integration. This prospective pilot study aimed to assess the sensorimotor integration and inhibitory circuitry in the sensorimotor cortex using short-latency afferent inhibition (SAI) paradigm in migraine. Methods Twenty-five migraine without aura patients (10 interictal, 5 preictal, 10 ictal) and 16 healthy controls were enrolled. SAI was elicited by combining the right median nerve electrical stimulation and left motor cortical magnetic stimulation at the 21-millisecond interval. Mean motor evoked potential (MEP) amplitude ratio, recorded from right abductor pollicis muscle after single and conditioned stimulations, was calculated as SAI. Results Average MEP inhibition ratio after single and conditioned stimuli in healthy controls was not significantly different from interictal patients (45.1% +/- 20.3% vs 44.5% +/- 14.75% [P = .93]). However, SAI was significantly reduced during preictal/prodromal (-14.6% +/- 42.8% [P = .002]) and ictal/headache (-7.4% +/- 31.1% [P = .0001]) periods of migraine compared to healthy controls. Conclusion Pronounced decrease in SAI during preictal and ictal periods in migraine was shown for the first time. Instead of inhibition to a conditioned stimulus, facilitation in the sensorimotor cortex was detected both ictally and preictally. Preictal SAI results suggest the presence of increased excitability state several hours prior to the headache phase. This phenomenon could be related to the cortical hyperresponsivity to sensory stimuli and cognitive disturbances accompanying migraine attacks as SAI is modulated by cholinergic activity.

BACKGROUND/AIM Chronic migraine is a common debilitating disease with limited treatment options. We aimed to develop a novel model for chronic migraine by ligating the nasociliary nerve (NCL) and administering nitroglycerin (NTG) to exacerbate acute headache attacks. MATERIALS AND METHODS Exacerbation of the headache was induced by NTG (10 mg/kg, subcutaneously) administered to male Wistar rats (n = 36) 14 days following unilateral NCL. Cutaneous and cold allodynia was tested using Von Frey (VF) filaments and acetone, respectively. Elevated plus maze (EPM) results and c-fos immunoreactivity of TNC were investigated. RESULTS NTG administration significantly decreased VF threshold values only in the nasociliary nerve (NCN) territory and the ipsilateral forepaw (P = 0.0001, P = 0.02). Cold allodynia developed in bilateral NCN territories (P = 0.013). The number/rate of entrance to open arms in the EPM was significantly decreased in NCN-ligated rats (P = 0.042, P = 0.035). Immunohistochemistry disclosed significantly increased c-fos-positive neurons in ipsilateral brainstem TNC compared to the contralateral side (brain stem LI ipsilateral 25.4 ± 4.7, contralateral 11.8 ± 1.9, P < 0.05) in chronic NCN-ligated rats exposed to acute NTG. CONCLUSION The presented model provides a valid chronic migraine model relevant to humans, as NTG challenge in chronic NCL rats generated lateralized headache with cephalic and extracephalic allodynia, altered cold sensitivity, anxiety, and neuronal activation in the nociceptive laminae of brainstem trigeminal pain nuclei.

Migraine is a common neurological disorder with significantly higher incidence and prevalence in women than men. The presentation of the disease in women is modulated by changes in sex hormones from adolescence to pregnancy and menopause. Yet, the effect of sex influences has often been neglected in both basic and clinical and in clinical management of the disease. In this review, evidence from epidemiological, clinical, animal, and neuroimaging studies on the significance of the sex-related influences in migraine is presented, and the unmet needs in each area are discussed. © 2016 Wiley Periodicals, Inc.

Background and objective Somatosensory temporal discrimination was recently reported as prolonged during migraine attacks, which is consistent with disrupted sensorial perception in migraine. However, knowledge about central sensory processing in tension-type headache is still lacking. This prospective, controlled study aimed to investigate somatosensory temporal discrimination thresholds in tension-type headache. Methods The study included 10 tension-type headache patients, 10 migraine patients and 10 healthy volunteers without headache. Somatosensory temporal discrimination thresholds were evaluated during the headache attacks of tension-type headache and migraine patients. Results Somatosensory temporal discrimination thresholds of tension-type headache patients (39.0 ± 5.5 ms for the right hand and 40.6 ± 4.6 ms for the left hand) were significantly lower than those of episodic migraine patients (137.1 ± 35.8 ms for the right hand and 118.4 ± 34.3 ms for the left hand, p Conclusion Central sensory processing, as tested by somatosensory temporal discrimination, was remarkably disrupted during the headache attacks in migraineurs, whereas it remained intact in the tension-type headache patients.

The functional anatomy of the trigeminal nerve and upper cervical nerves in transmitting head and neck pain is briefly reviewed. The chapter will focus on specific structures that interventional approaches target in headache management. The aim is to provide a general view and an understanding of the mechanisms underlying peripheral nerve interventions in clinical practice.

Animal models have provided a growing body of information about the pathophysiology of headaches and novel therapeutic targets. In recent years, experiments in awake animals have gained attention as more relevant headache models. Pain can be assessed in animals using behavioral alterations, which includes sensory-discriminative, affective-emotional and cognitive aspects. Spontaneous behavioral alterations such as increased grooming, freezing, eye blinking, wet dog shake and head shake and decreased locomotion, rearing, food or water consumption observed during pain episodes are oftentimes easy to translate into clinical outcomes, but are giving little information about the localization and modality of the pain. Evoked pain response such as tactile and thermal hypersensitivity measures are less translatable but gives more insight into mechanisms of action. Mechanical allodynia is usually assessed with von Frey monofilaments and dynamic aesthesiometer, and thermal allodynia can be evaluated with acetone evaporation test and Hargreaves’ test in animal models. Anxiety and depression are the most frequent comorbid diseases in headache disorders. Anxiety-like behaviors are evaluated with the open-field, elevated plus-maze or light/dark box tests. Interpretation of the latter test is challenging in migraine models, as presence of photophobia or photosensitivity can also be measured in light/dark boxes. Depressive behavior is assessed with the forced-swim or tail suspension tests. The majority of headache patients complain of cognitive symptoms and migraine is associated with poor cognitive performance in clinic-based studies. Cluster headache and tension type headache patients also exhibit a reversible cognitive dysfunction during the headache attacks. However, only a limited number of animal studies have investigated cognitive aspects of headache disorders, which remains a relatively unexplored aspect of these pathologies. Thus, the headache field has an excellent and growing selection of model systems that are likely to yield exciting advances in the future.

An international committee set up through the IAP for Healthmet to develop an action plan for dementia. Comprehensiveinternational and national initiatives should move forwardwith calls for action that include increased public awarenessregarding brain health and dementia, support for a broad rangeof dementia research objectives, and investment in nationalhealth care systems to ensure timely competent person-centredcare for individuals with dementia. The elements of suchaction plans should include: 1) Development of national plansincluding assessment of relevant lifecourse risk and protectivefactors; 2) Increased investments in national research programson dementia with approximately 1% of the national annual costof the disease invested; 3) Allocating funds to support a broadrange of biomedical, clinical, and health service and systemsresearch; 4) Institution of risk reduction strategies; 5) Buildingthe required trained workforce (health care workers, teachers,and others) to deal with the dementia crisis; 6) Ensuring that itis possible to live well with dementia; and 7) Ensuring that allhave access to prevention programs, care, and supportive livingenvironments.