OBJECTIVE: To analyze the prevalence and burden of headache disorders in China and its provinces from 1990 to 2021. METHODS: Using data from the Global Burden of Disease Study (GBD) 2021, the number of prevalent cases, prevalence rate, disability-adjusted life years (DALYs), and age-standardized DALY rates were analyzed by sex, age group, and province for headache disorders and their subtypes (migraine and tension-type headache [TTH]) between 1990 and 2021. Percentage changes during this period were also estimated. RESULTS: In 2021, approximately 426 million individuals in China were affected by headache disorders, with an age-standardized prevalence rate of 27,582.61/100,000. The age-standardized DALY rate for all headache disorders was 487.15/100,000. Between 1990 and 2021, the number of prevalent cases increased by 37.78%, while the prevalence of all headache disorders, migraine, and TTH increased by 6.92%, 7.57%, and 7.86%, respectively. The highest prevalence was observed in the 30-34 age group (39,520.60/100,000). Migraine accounted for a larger proportion of DALYs attributable to headache disorders, whereas TTH has a greater impact on its prevalence. In 2021, the highest age-standardized DALY rates for headache disorders were observed in Heilongjiang (617.85/100,000) and Shanghai (542.86/100,000). CONCLUSION The prevalence of headache disorders is increasing in China. Effective health education, improve diagnosis and treatment are essential, particularly for middle-aged working populations and women of childbearing age.
Humans ; China/epidemiology* ; Female ; Male ; Adult ; Middle Aged ; Prevalence ; Young Adult ; Adolescent ; Aged ; Child ; Headache Disorders/epidemiology* ; Disability-Adjusted Life Years ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over

Headaches are among the top reasons for consultation in primary care clinics and can be classified either as primary or secondary. Primary headaches are unrelated to any medical condition and usually benign in nature. Secondary headaches are caused by an underlying pathology or condition. The mnemonic “HEADACHES” may be used to remember the red flags and it includes: Headache of sudden onset, Elderly onset, Altered mental status or neurologic deficits, Different or new pattern, Associated systemic symptoms, Cancer or immunocompromised state, Headache with exertion or position change, Eye findings and Secondary risk factors. Patients presenting with red flags are suggested to have underlying causes or secondary headaches and presence of which warrants diagnostic investigation or referral to specialists. Diagnostic imaging is not routinely recommended for patients with headache unless presenting with red flags or with suspected underlying pathology.

OBJECTIVES: To investigate the role of a neural pathway from oxytocin (OXT) neurons in the paraventricular hypothalamic nucleus (PVN) to γ-aminobutyric acid (GABA) neurons (GABAergic neurons) in the trigeminal nucleus caudalis (TNC) in regulating pain sensitization in a mouse model of chronic migraine and to explore the underlying mechanisms. METHODS: A chronic migraine mouse model was established by intraperitoneal injection of nitroglycerin (NTG, 1 mg/mL, 10 mg/kg) on days 1, 3, 5, 7, and 9. The study consisted of four parts: PartⅠ: 24 male wild-type C57BL/6J mice were divided into four groups (n=6 in each), receiving single or repeated injection of NTG or saline, respectively. Immunofluorescence was used to detect c-Fos and OXT expression in the PVN. Part Ⅱ: 6 male OXT-Cre transgenic C57BL/6J mice were used for anterograde monosynaptic tracing combined with RNAscope and immunofluorescence to identify neural projections from PVN OXT neurons to TNC GABAergic neurons. Part Ⅲ: 30 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into five groups, with six mice in each group. Mice in the clozapine N-oxide (CNO) group and the control group were intra-peritoneally injected with 0.1 mg/mL of CNO solution (1 mg/kg) and the same volume of isotonic normal saline, respectively. 3 hours after the injection, the brain tissues were harvest and c-Fos immunofluorescence staining was performed to verify the efficiency of chemogenetic activation virus. Mice in the model control group and the CNO activated model group were subjected to chronic migraine modeling, with bilateral TNC injection of isotonic normal saline and CNO, respectively, on day 10. The mice in the negative control group were bilaterally intra-TNC injected with isotonic normal saline. After 30 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice in these three groups. Part Ⅳ: 24 male OXT-Cre transgenic C57BL/6J mice were bilaterally injected with the Cre-dependent chemogenetic activation virus into the PVN. These mice were randomly divided into four groups, with six mice in each group. Mice in the model control group, the CNO activated model group and the atosiban group were subjected to chronic migraine modeling. On day 10, mice in the negative control group and the model control group were intraperitoneally injected with isotonic normal saline, while mice in the CNO activated model group and the atosiban group were intraperitoneally injected with CNO. After 15 minutes, mice in the atosiban group were bilaterally intra-TNC injected with atosiban, while mice in other three groups were bilaterally intra-TNC injected with isotonic normal saline containing 1% dimethyl sulfoxide. After 15 minutes, the Von-Frey filament and acetone tests were used to assess the mechanical pain threshold and cold pain response time in the periorbital region of the mice. The GABA content in the bilateral TNC was detected by high-performance liquid chromatography (HPLC). RESULTS: Mice with chronic migraine models exhibited reduced periorbital mechanical pain thresholds and increased periorbital cold pain reaction time, accompanied by an increase in both the number of c-Fos⁺ neurons and the percentage of c-Fos⁺ OXT neurons in the PVN (all P<0.05). The anterograde tracing virus and RNAscope combined with immunofluorescence staining showed that PVN OXT neurons projected to TNC GABAergic neurons. Immuno-fluorescence staining demonstrated that compared with the control group, the percentage of c-Fos⁺ OXT neurons in the PVN of CNO group increased (P<0.05). In bilateral intra-TNC drug administration experiments, compared with the model control group, the periorbital mechanical pain threshold increased, and the periorbital cold pain reaction time decreased in the CNO activated model group (both P<0.05). In intraperitoneal drug administration experiments, compared with the CNO activate model group, the periorbital mechanical pain threshold decreased, and the periorbital cold pain reaction time increased in the atosiban group (both P<0.05). HPLC analysis showed that, compared with the negative control group, the model control group and the atosiban group, GABA level of TNC in the CNO activated model group increased (all P<0.05). CONCLUSIONS PVN OXT neurons exert a descending facilitatory effect on GABAergic neurons in the TNC via OXT release, thereby ameliorating pain sensitization in chronic migraine.
Animals ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Male ; Mice, Inbred C57BL ; Migraine Disorders/physiopathology* ; Mice ; GABAergic Neurons/physiology* ; Oxytocin/physiology* ; Disease Models, Animal ; Neurons/physiology* ; Mice, Transgenic ; Neural Pathways ; Chronic Disease

OBJECTIVE: To investigate the effect and safety of phytosomal curcumin supplementation on patients with migraine. METHODS: In this randomized, double-blind and placebo-controlled trial, 70 patients suffered from migraine without aura were randomized into 2 groups to receive 250 mg/d of phytosomal curcumin (intervention group) or maltodextrin (placebo group) for 8 weeks, 35 cases per group. All patients in both groups received their standard treatment and common medications. The severity, duration, frequency of headaches, quality of life (QoL), mental status, headache impact, and sleep quality of patients were assessed before and after treatment. Adverse effects were also assessed. RESULTS: Sixty-five patients completed the trial (33 in the intervention group and 32 in the placebo group). Phytosomal curcumin supplementation significantly reduced severity, duration and frequency of migraine attacks, stress score, and headache impact, and improved QoL and sleep quality of patients in the intervention group, compared with the placebo group (P<0.05 or P<0.01). However, it had no significant effect on depression and anxiety scores in the intervention group, compared with the placebo group (P>0.05). No adverse effects had been reported in response to the intervention. CONCLUSION Phytosomal curcumin as a safe supplement had a beneficial effect on migraine symptoms, stress level, as well as the sleep quality and QoL in patients with migraine. (Trial registration No. IRCT20201129049534N2).
Humans ; Curcumin/adverse effects* ; Double-Blind Method ; Male ; Female ; Dietary Supplements/adverse effects* ; Migraine Disorders/drug therapy* ; Adult ; Quality of Life ; Middle Aged ; Placebos ; Treatment Outcome

Objective:To investigate the sleep characteristics and clinical features of patients with vestibular migraine（VM）, and to explore the influencing factors of sleep disorder in VM patients. Methods:A cross-sectional study method was adopted to collect VM patients from Otolaryngology department and neurology department of our hospital from June 2022 to June 2024（divided into sleep disorder group and non-sleep disorder group according to whether there is sleep disorder） as the experimental group, and recruit non-VM volunteers with clinical characteristics matching with the experimental group during the same period as the control group. The clinical data of the subjects were collected, and the sleep quality of the subjects was assessed using the Pittsburgh Sleep Quality Index（PSQI）. The influencing factors of sleep disorders in VM patients were analyzed by multivariate Logistic regression, and the correlation between sleep disorders and clinical features such as headache, vertigo and hearing in VM patients was analyzed by Spearman correlation coefficient. Results:A total of 530 individuals with VM were analyzed, including 332 with sleep disturbances（62.64%）, 198 without sleep issues（37.36%）, and 50 in the control group. The overall PSQI score and all its components were significantly higher in the VM group compared with the control group（P<0.05）. A positive correlation was observed between PSQI and VAS, DHI-T, DHI-E, DHI-F and DHI-P（r=0.797, P<0.05; r=0.834, P<0.05; r=0.794, P<0.05; r=0.771, P<0.05; r=0.877, P<0.05）, PSQI had no correlation with pure tone hearing（r=0.324, P=0.167）. Multivariate logistic regression analysis showed that female, age ≥60 years, living alone, duration of disease ≥3 months, motion sickness history, and HADS-A were independent influencing factors for comorbidification of sleep disorder in VM patients（P<0.05）. Conclusion:The prevalence of sleep disorders in patients with vestibular migraine（VM） was significantly higher compared to the control group. Moreover, the severity of sleep disorders was positively correlated with the intensity of headache and vertigo in VM patients. It is recommended that female VM patients aged 60 years or older, living alone, with a disease duration of three months or longer, a history of motion sickness, and anxiety symptoms undergo sleep assessments to determine the presence of sleep disorders. This approach provides a theoretical foundation for precise treatment and prevention strategies for VM.
Humans ; Migraine Disorders/complications* ; Sleep Wake Disorders/complications* ; Cross-Sectional Studies ; Vertigo ; Female ; Male ; Vestibular Diseases/complications* ; Sleep Quality ; Adult ; Middle Aged ; Logistic Models

Objective:To analyze the clinical characteristics and prognostic factors of patients with acute low-frequency hearing loss（ALHL） and explore the potential role of migraine in its pathogenesis. Methods:A total of 56 ALHL patients treated at our outpatient clinic from June 2024 to January 2025 were randomly divided into two groups: a standardized treatment group and an anti-migraine treatment group. The standardized group received oral/intravenous steroids + oral/intravenous Ginkgo biloba extract, while the anti-migraine group received postauricular steroid injection/oral steroids + oral flunarizine for 2 weeks. Audiological, clinical, and psychological characteristics were collected, and statistical analysis was performed to assess clinical features and treatment outcomes, exploring the potential mechanism of migraine in ALHL. Results:The anti-migraine treatment group showed a significantly higher recovery rate than the standardized treatment group（92.86% vs 71.43%, P=0.036）. Among the anti-migraine group, 6 patients（21.43%） had a history of ALHL, 13（46.43%） had a confirmed migraine history, 26（92.86%） had anxiety, 26（92.86%） had depression, 5（17.86%） had irritable bowel syndrome, 21（75.00%） had sleep disorders, and 1（3.57%） experienced recurrence within 6 months. Conclusion:Anti-migraine therapy significantly improves the recovery rate in ALHL patients, suggesting that migraine may have a certain correlation with the pathogenesis of acute low-frequency hearing loss.
Humans ; Migraine Disorders/complications* ; Ginkgo biloba ; Male ; Female ; Flunarizine/therapeutic use* ; Plant Extracts/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Ginkgo Extract

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

Objective:The clinical significance of aural fullness in patients with vestibular migraine（VM） remains unclear, and it is yet to be determined whether VM with aural fullness represents a distinct subtype of VM; this study aimed to compare differences in demographic characteristics, clinical manifestations, audiological findings, and vestibular function tests between VM patients with and without aural fullness, and explore whether the former is a subtype of VM and whether it requires differentiated treatment. Methods:A total of 174 VM patients were enrolled, including 75 with aural fullness（aural fullness group） and 99 without aural fullness（non-aural fullness group）; demographic data, vertigo characteristics, medical history, family history, pure-tone audiometry, and vestibular function tests were thoroughly recorded, and independent samples t-test and chi-square test were used for inter-group comparisons. Results:①Regarding demographic characteristics, the age of the aural fullness group was significantly lower than that of the non-aural fullness group[（44.08±13.97） years vs. （49.45±16.05） years, P=0.020）, while the two groups showed consistent gender distribution（more females than males） with no statistically significant difference. ②For aural fullness characteristics, unilateral aural fullness accounted for 65.0% in the aural fullness group, significantly higher than bilateral aural fullness（35.0%, P<0.001）. ③In terms of vertigo characteristics, there were no statistically significant inter-group differences in the nature of attacks（rotational vertigo: 36.0% vs. 41.4%, P=0.463; dizziness: 21.3% vs. 11.1%, P=0.064; rotational vertigo or dizziness: 29.3% vs. 25.3%, P=0.548; dizziness with unsteady gait: 9.3% vs. 11.1%, Fisher P=0.806; visual oscillation with unsteady gait: 4.0% vs. 11.1%, Fisher P=0.086）, duration（several hours: 34.7% vs. 33.3%, P=0.841; several minutes: 22.7% vs. 21.2%, P=0.808; several seconds: 5.3% vs. 8.1%, Fisher P=0.557; several days: 9.3% vs. 9.1%, Fisher P=1.000; multiple combined patterns: 17.3% vs. 15.2%, P=0.686）, or incidence of nausea and vomiting（84.0% vs. 72.7%, P=0.071, no statistical significance）. ④No statistically significant inter-group differences were found in medical history and family history, including motion sickness history（8.0% vs. 4.0%, Fisher P=0.337）, headache history（22.7% vs. 34.3%, P=0.084）, and family history of dizziness（12.0% vs. 14.1%, P=0.666）. ⑤For audiological characteristics, 21.3%（16/75） of patients in the aural fullness group had low-frequency hearing loss, significantly higher than 5.1% in the non-aural fullness group（χ²=10.66, P=0.001）; among patients with unilateral aural fullness, 28.6%（14/49） had ipsilateral low-frequency hearing loss, significantly higher than 7.7%（2/26） of those with bilateral aural fullness（χ²=4.41, P=0.036）; however, there was no statistically significant difference in the rate of bilateral high-frequency hearing loss between the two groups（54.7%[41/75]vs. 50.5%[50/99], χ²=0.30, P=0.586）. ⑥In vestibular function tests, no statistically significant inter-group differences were observed in smooth pursuit type Ⅲ/Ⅳ（12.5% vs. 13.1%, P=0.913）, caloric test with CP>25%（31.2% vs. 37.4%, P=0.411）, abnormal video head impulse test（vHIT） rate（30.8% vs. 32.6%, P=0.865）, or abnormal vestibular evoked myogenic potential（VEMP） rate（53.8% vs. 38.9%, Fisher P=0.484）. Conclusion:VM patients with aural fullness have an earlier age of onset, with nearly 1/4 accompanied by low-frequency hearing loss; VM patients with and without aural fullness are highly consistent in gender distribution, nature/duration of vertigo, vestibular function impairment, and presence of bilateral high-frequency hearing loss, suggesting that the core clinical phenotypes of the two groups are consistent, while the former has an earlier age of onset and a higher proportion of unilateral hearing loss, which may be related to the pathological mechanism of VM and inner ear microcirculation disorders.
Humans ; Female ; Male ; Middle Aged ; Adult ; Migraine Disorders/classification* ; Young Adult ; Vertigo ; Age of Onset ; Aged ; Hearing Loss

OBJECTIVES: To investigate the therapeutic mechanism of Huoxue Shufeng Granules (HXSFG) for alleviating central sensitization in a mouse model of chronic migraine (CM). METHODS: We analyzed the main chemical components of HXSFG through literature review and explored their pharmacological mechanisms by bioinformatics analyses. In a male C57BL/6J mouse model of CM established by intraperitoneal injections of nitroglycerin (10 mg/kg) every other day (5 injections), the effects of gavage with low, and high doses of HXSFG or intraperitoneal injections of topiramate for ameliorating central sensitization were evaluated using Von Frey test and a hot plate apparatus; the changes in expressions of inflammatory factors, the proteins in the TLR4/NF‑κB signaling pathway, and activation of c-Fos and CGRP were detected using RT-qPCR, Western blotting and immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that the main active components in HXSFG for alleviating CM included formononetin, paeoniflorin, quercetin, and tanshinone. Gene Ontology (GO) enrichment analysis identified 492 GO entries, comprising 366 biological processes, 46 cellular components, and 80 molecular functions. KEGG pathway enrichment analysis indicated that the Toll-like receptor and NF‑κB signaling pathways were crucial in mediating the therapeutic effects of HXSFG on CM. In the mouse models of CM, both topiramate and HXSFG treatments alleviated the symptoms of central sensitization, evidenced by improved mechanical and thermal pain thresholds in the mice. HXSFG significantly reduced the expression of c-Fos and CGRP, improved inflammatory markers, and downregulated the expressions of TLR4, p-NF‑κB, IL-1β, and TNF‑α proteins in the mouse models. CONCLUSIONS HXSFG effectively alleviates central sensitization in CM mice by modulating the inflammatory pathways and inhibiting the TLR4/ NF-κB signaling pathway, suggesting its potential as a therapeutic option for CM.
Animals ; Toll-Like Receptor 4/metabolism* ; NF-kappa B/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Male ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Migraine Disorders/metabolism* ; Disease Models, Animal ; Inflammation

Various acupuncture clinical trials have been conducted on migraine; however, the conclusions remain controversial especially when acupuncture was compared with sham acupuncture. Sham acupuncture is sometimes performed at the same acupuncture points used for verum acupuncture despite the evidence on acupuncture point specificity. Four databases were searched for sham acupuncture or waiting list-controlled acupuncture trials for migraine on December 25, 2023. Sham acupuncture was classified according to the needling points: sham acupuncture therapy at verum points (SATV) or at sham points (SATS). Network meta-analysis was performed based on the frequentist framework for headache pain intensity and response rate. A total of 18 studies involving 1936 participants were analyzed. Headache pain intensity and response rate were significantly improved in verum acupuncture compared with SATS. However, there was no significant difference between SATV and verum acupuncture. When comparing SATS and SATV, there was no significant difference in headache pain intensity and response rate; however, the results were in favor of SATV. The effect of the risk of bias on the certainty of evidence between verum and sham acupunctures was judged to be generally low. SATV should not be misused as a placebo control to evaluate the efficacy of acupuncture.
Humans ; Migraine Disorders/therapy* ; Acupuncture Therapy/methods* ; Acupuncture Points ; Treatment Outcome ; Randomized Controlled Trials as Topic