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Background: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets., Methods: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST., Results: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05)., Conclusions: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC., (© 2024. The Author(s).)

Background: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood., Methods: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats., Results: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application., Conclusions: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future., (© 2024. The Author(s).)

Background: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM., Methods: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention., Results: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway., Conclusions: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine., (© 2024. The Author(s).)

Background: Headache during hemodialysis (HDH) is prevalent but not negligible. Despite the high prevalence of dialysis headaches, they have rarely been studied. Therefore, this study aimed to evaluate the prevalence, risk factors, and clinical characteristics of HDH and reappraise the HDH diagnostic criteria in the International Classification of Headache Disorders 3 (ICHD-3)., Methods: One hundred and fifty-four patients completed this randomized cross-sectional study. Consecutive patients who underwent haemodialysis were assessed using a semi-structured questionnaire. The patients were administered face-to-face questionnaires while undergoing dialysis., Results: This study included 154 patients. Before commencing dialysis, 3.24% (5/154) of the patients had migraine without aura, 1.29% (2/154) had menstrual-related migraine, 0.6% (1/154) had tension-type headaches, and 0.6% (1/154) had an unclassifiable headache. One case (0.6%) of headache resolved after dialysis treatment. HDH was diagnosed in 9.09% (14/154) of the patients. Headache after haemodialysis (HAH) was reported in 6.49% (10/154) of patients. The most prevalent features of HDH were frontal or temporal location, bilateral headaches, dull and throbbing nature, and moderate severity. HDH started at a mean of 2.33 ± 0.79 h after dialysis commenced. The average headache duration was 6.56 ± 1.57 h (median = 3.0 h), with 66.67% of the patients reporting a duration of ≤4 h. HDH was more prevalent in females than males (P = 0.01, P < 0.05). Female sex was a risk factor for HDH (P = 0.01，P < 0.05)., Conclusions: The diagnostic criteria for 10.2 HDH in ICHD-3 may miss several HAH. Therefore, ICHD-3 should be revised according to the literature and further studies., (© 2023. The Author(s).)

Background: Angiography headache (AH) is common but not negligible, and the criteria for AH have been based on only a few studies. The purpose of this study was to investigate the incidence, risk factors and possible mechanism of AH and reappraise the diagnostic criteria for AH in the International Classification of Headache Disorders 3 (ICHD-3)., Methods: Two hundred and seventy-nine patients completed this prospective, non-randomized study, including 107 patients who underwent cerebral angiography, 101 patients who underwent coronary intervention and 71 patients who underwent extremities arterial intervention. Patients were followed up with questionnaires immediately after the procedure and 24 h, 72 h, 1 week and 2 weeks after the procedure., Results: The incidence of headache was 22.4% (24/107) in cerebral angiography group, 23.8% (24/101) in coronary intervention group, and 16.9% (12/71) in extremities arterial intervention group. Headache still occurred in 12.1% (13/107), 14.9% (15/101) and 11.3% (8/71) of patients 24 h after the procedure in the three groups, respectively. Two types of headache were observed in cerebral angiography group and coronary intervention group, one during and one after the procedure, while only postoperative headache was observed in extremities arterial intervention group. Previous headache history was a risk factor for headache in the three groups (p = 0.003 in cerebral angiography group, p = 0.006 in coronary intervention group, and p = 0.016 in extremities arterial intervention group). In addition, female (p = 0.008) was a risk factor for cerebral angiography group. Headache characteristics were described in detail., Conclusions: The diagnostic criteria for 6.7.2 angiography headache in ICHD-3 may miss a number of cerebral AH with onset later than 24 h after the procedure. Therefore, it is recommended to revise it according to the literature and further studies. The incidence of headache was high during and after angiography and interventional procedure. It was suggested that the definition of headache due to coronary intervention and headache due to extremities arterial intervention should be added in ICHD., (© 2021. The Author(s).)

Background: Astrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release., Methods: We used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A)., Results: Recurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d., Conclusions: Our results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release., (© 2022. The Author(s).)

Background: Mutations in ATP1A2, the gene encoding the α2 subunit of Na + /K + -ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear., Methods: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na + /K + -ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations., Results: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na + /K + -ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na + /K + -ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na + /K + -ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain., Conclusions: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na + /K + -ATPase. Mutations associated with intellectual disability presented with severe impairment of Na + /K + -ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function., (© 2021. The Author(s).)

Background: A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time., Methods: Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire., Results: Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH., Conclusion: The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Background: Migraine and Tension-type headache (TTH) are common and disabling primary headache disorders. They are more prevalent in females. The second to fourth digit ratio (2D:4D) is sexually dimorphic in humans and is considered to be a marker for the balance of prenatal testosterone and estrogen exposure. Therefore, we investigated the hypothesis that prenatal sex steroids constitute an independent risk factor for adult headaches later in life., Methods: A total of 891 individuals (303 males, 588 females) of 18-68 years in age (a mean of 37.0 ± 10.1 years), including 279 migraine, 300 TTH, and 312 healthy subjects were enrolled. The 2D:4D ratio was measured by a single investigator using a digital Vernier caliper., Results: The females in the migraine group had lower 2D:4D ratios than those in the control group (left hand: 0.947 ± 0.034 vs. 0.955 ± 0.038, p = 0.048; right hand: 0.952 ± 0.035 vs. 0.965 ± 0.037, p = 0.001). There was a similar relationship between the TTH group and the control group (left hand: 0.946 ± 0.034 vs. 0.955 ± 0.038, p = 0.034; right hand: 0.954 ± 0.035 vs. 0.965 ± 0.037, p = 0.005), although this was not observed in males. Males showed lower 2D:4D ratios than females for the right hand in the control group (0.954 ± 0.039 vs. 0.965 ± 0.037, p = 0.015). No significant difference was found in the left hand., Conclusions: These results suggested that the 2D:4D ratio is a risk factor of migraine and TTH and that the balance of prenatal estrogen and testosterone in utero may impact adult primary headache disorders.

Background: Receptor activity modifying protein 1(RAMP1) is a key receptor subunit of calcitonin gene related peptide (CGRP) playing a critical role in migraine. But variations in RAMP1 gene have not been found to link with migraine. Still it is elusive that DNA methylation at RAMP1 promoter is associated with migraine., Methods: A total of 51 blood DNA samples from 26 patients with migraine and 25 matched healthy controls were collected, extracted and treated with bisulfate. Subsequently DNA methylation levels at RAMP1 promoter region were measured using Sequenom Mass ARRAY systems., Results: Among 13 detected CpG sites or units at RAMP1 promoter region, there were no significant differences between the migraine and control groups, but indicating a low methylation trend overall in migraine group (total average methylation level: 8.41 % ±1.92 % vs. 9.90 % ± 3.88 %, p = 0.197). Stratification analysis showed that methylation level at (+25, +27, +31, related to the transcription start site) CpG unit was higher in migraineurs with migraine family history compared to those without (13.92 % ± 5.97 % vs. 8.77 % ± 6.61 %, p = 0.034), and methylation level at (+89, +94, +96) CpG unit was lower in migraine female than that in healthy female (2.18 % ± 1.91 % vs. 5.85 % ± 5.41 %, p = 0.02). For female with methylation level at (+89, +94, +96) CpG unit below 3.50 %, the probability of being a migraine patient was significantly higher than those with methylation level above the threshold (OR: 7.313; 95%CI: 1.439-37.164)., Conclusions: This study provides the first evidence that DNA methylation at RAMP1 promoter might play a role in migraine. A low methylation trend overall was presented in migraine subjects, and two CpG units were observed to link with positive migraine family history and female migraine, respectively. Lower methlytion level at (+89, +94, +96) CpG unit may be a risk of migraine in females.

Background: Both hypertension (HTN) and headache disorders are highly prevalent worldwide. Our purpose, in a nationwide study of the Chinese general population, was to evaluate any association between primary headache disorders and elevated blood pressure (eBP). We could not collect data on antihypertensive therapy, but took the view that, whatever such therapy might be taken, eBP was a sign that it was failing to meet treatment needs. Therefore, as a secondary purpose, important from the public-health perspective, we would present the prevalence of eBP (treated or not) as indicative of unmet health-care need in China., Methods: This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18-65 years) per household. Headache was diagnosed by ICHD-II criteria and eBP as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. We set significance at P ≤ 0.05., Results: Of 5,041 survey participants (participation rate 94.1 %), 154 were excluded because of missing BP data, leaving 4,987 for analysis [mean age: 43.6 ± 12.8 years; male 2,532 (mean age: 43.4 ± 12.9 years); female 2,455 (mean age 43.9 ± 12.8 years)]. There were 466 participants with migraine, 535 with tension type headache (TTH) and 48 with all causes of headache on ≥15 days/month. The prevalence of eBP was 22.1 % (males 22.9 %, females 21.3 %). No associations of eBP with any of the headache disorders survived multivariate adjusted analysis. The demographic and anthropometric variables most strongly associated with eBP were higher age (AOR 3.7) and being overweight (AOR 2.4), seen in both genders. Less strong were male gender, lower educational level and urban habitation., Conclusions: We found no clear-cut associations between eBP and any headache disorder. The associations with demographic and anthropometric variables may have acted as confounders in past reports to the contrary. We did find an alarmingly high prevalence of eBP, recognizing that this signals substantial under-treatment in China of a serious condition, and therefore a major public-health concern.

Background: The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Event-related potentials confer advantages in the functional evaluation of the cortex, but few studies thus far have employed this method in cluster headache., Methods: Seventeen cluster patients (15 males; mean age = 35.4 years) and 15 age-matched healthy participants (13 males; mean age = 34.6 years) were recruited. A visual oddball paradigm was employed to analyze target processing using event-related potentials. We investigated the P3/P3d components in the experiment., Results: P3/P3d amplitudes were decreased in CH patients (P3, 3.82 μV; P3d, 5.8 μV) compared with controls (P3, 7.28 μV; P3d, 8.95 μV), F(1,30) = 4.919, p < 0.05, η2 = 0.141 for P3 and F(1,30) = 8.514, p < 0.05, η2 = 0.221 for P3d, respectively). Moreover, the amplitudes of P3/P3d were no significantl difference in the side of pain as compared to contralateral one (p > 0.05)., Conclusions: These results provide evidence of dysfunction in the cognitive processing of CH patients, which may also contribute to the pathophysiology of CH.

Background: In order to know the status quo of health care for primary headache disorders in China, questions about headache consultation and diagnosis were included in a nationwide population-based survey initiated by Lifting The Burden: the Global Campaign against Headache., Methods: Throughout China, 5,041 unrelated respondents aged 18-65 years were randomly sampled from the general population and visited unannounced at their homes. After basic sociodemographic and headache diagnostic questions, respondents with headache answered further questions about health-care utilization in the previous year., Results: Significantly higher proportions of respondents with migraine (239/452; 52.9%) or headache on ≥15 days per month (23/48; 47.9%) had consulted a physician for headache than of those with tension-type headache (TTH) (218/531; 41.1%; P < 0.05). Multivariate analysis showed associations between disability and probability of consultation in those with migraine (mild vs. minimal: AOR 3.4, 95% CI: 1.6-7.4; moderate vs. minimal: 2.5, 1.2-5.4; severe vs. minimal: 3.9, 1.9-8.1) and between rural habitation and probability of consulting in those with TTH (AOR: 3.5; 95% CI: 1.9-6.3, P < 0.001). Married respondents with TTH were less likely than unmarried to have consulted (AOR: 0.26; 95% CI: 0.07-0.93; P = 0.038). About half of consultations (47.8-56.5%) for each of the headache disorders were at clinic level in the health system. Consultations in level-3 hospitals were relatively few for migraine (5.9%) but more likely for headache on ≥15 days/month (8.7%) and, surprisingly, for TTH (13.3%). Under-diagnosis and misdiagnosis were common in consulters. More than half with migraine (52.7%) or headache on ≥15 days/month (51.2%), and almost two thirds (63.7%) with TTH, reported no previous diagnosis. Consulters with migraine were as likely (13.8%) to have been diagnosed with "nervous headache" as with migraine. "Nervous headache" (9.8%) and "vascular headache" (7.6%) were the most likely diagnoses in those with TTH, of whom only 5.6% had previously been correctly diagnosed. These were also the most likely diagnoses (14.0% each) in consulters with headache on ≥15 days/month., Conclusions: This picture of the status quo shows limited reach of headache services in China, and high rates of under-diagnosis and misdiagnosis in those who achieve access to them. This is not a picture of an efficient or cost-effective response to major causes of public ill-health and disability.

Background: The clinical profile of cluster headache in Chinese patients have not been fully studied., Methods: The classification and clinical features of 120 consecutive patients with cluster headache (105 males, 15 females; mean age, 34.9 ± 10.5 years) visiting at International Headache Center from May 2010 to August 2012 were analyzed., Results: Patients came from 16 different regions of China. Mean age at onset of cluster headache was 26.7 ± 10.9 years. Only 13 patients (10.8%) had previously been diagnosed with cluster headache. Mean time to diagnosis from first symptoms was 8.2 ± 7.1 years (range, 0-35 years). Chronic cluster headache was observed in only 9 patients (7.5%). The most commonly reported location of cluster headache was temporal region (75.0%), followed by retro-orbital region (68.3%), forehead (32.5%), vertex (32.5%) and occipital (22.5%). Lacrimation was the most consistently reported autonomic feature (72.5%). During acute attacks, 60.0% of patients experienced nausea, and 41.7% experienced photophobia and 40.8% experienced phonophobia. In addition, 38.3% reported restless behavior and 45.8% reported that physical activity exacerbated the pain. None of patients experienced visual or other kinds of aura symptoms before cluster attacks. We found that 38.3% of patients had <1 cluster period and 35.8% for 1-2 cluster periods per year with these periods occurring less frequently during the summer than during other seasons. Cluster duration was 1-2 months in 32.5% of patients. During cluster periods, 73.3% of patients had 1-2 attacks per day, and 39.2% experienced cluster attacks ranging in duration from 1 h to less than 2 h. The duration of attacks were 1.5 (1-2.25) hours for males and 1.5 (1-3) for females respectively. The World Health Organization quality of life-8 questionnaire showed that cluster headache reduced life quality., Conclusions: Compared to Western patients, Chinese patients showed a relatively low prevalence of chronic cluster headaches, pain sites mainly focused on areas distributed by the first division of the trigeminal nerve, a low frequency of restlessness and absent aura. These clinical features may be more common in Eastern populations, including mainland Chinese, Japanese and Taiwanese patients, than in Western patients.

The objective of this study is to evaluate the association between body mass index (BMI) and migraine in general population Chinese cohort. This was a cross-sectional secondary analysis from a general population Chinese cohort of men and women of reproductive and post-reproductive age ranging between 18 and 65 years. Migraine was defined utilizing ICHD criteria. Body mass indices were calculated using measured height and weight and categorized based on the World Health Organizations criteria. The 1-year period prevalence of migraine was 9.3 %. No association was identified between migraine and those with a BMI < 30.0. Compared to those with normal BMI (18.5-23.0), those with BMI ≥ 30 (morbid obesity) had a greater prevalence of migraine (8.6 vs. 13.8 %, p = 0.000). Multivariate-adjusted odds ratio demonstrated that those with morbid obesity had a greater than twofold increased odds of migraine [OR 2.10 (1.39-3.12)] as compared to those with a BMI between 18.5 and 23.0. No association was found between obesity and migraine severity, frequency, or disability. Morbid obesity was associated with twofold increased odds of migraine in this Chinese men and women cohort of predominantly reproductive age.

A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O(2) inhalation before NaCl injections (Group V); 14% O(2) inhalation followed by KCl injections (Group VI); 14% O(2) inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions.