Journal of Headache and Pain最新文献

Background: Migraine is a common, disabling neurological disorder. Genome-wide association studies have mapped numerous migraine risk loci, but the causal genes and their cell-type context remain unclear. Prior work linked migraine GWAS to bulk brain eQTLs; however, tissue-average signals obscure cell-specific regulation.

Methods: We extended these findings to single-cell resolution. Cis-eQTL instruments from 183 human donors across eight brain cell types were filtered by genome-wide significance, LD pruning, and instrument strength, yielding 1,746 independent eGenes. Two-sample Mendelian randomization (MR) tested effects on migraine risk in FinnGen R12 (discovery) with replication in UK Biobank (GCST90473326). To control for multiple testing, we applied within-cell-type Bonferroni correction and global false discovery rate (FDR) adjustment. Bayesian colocalization was performed in both discovery and replication cohorts to evaluate shared causal variants. We also performed a phenome-wide association screen (PheWAS) and profiled regional brain RNA.

Results: Eleven eGenes were significant in FinnGen. Protective associations were observed for BTBD16 in excitatory and inhibitory neurons, RRP15 in excitatory neurons, CCDC146 and GSTM3 in oligodendrocytes, and PDE4B in microglia. Risk-increasing associations were found for GSTM2 (excitatory neurons), RIMS1 and DPH1 (astrocytes), AADAC (microglia), and RBM20 (endothelium). Replication supported signals for inhibitory-neuronal BTBD16 and astrocytic RIMS1. Colocalization analyses indicated shared causal variants at both loci in the discovery cohort (PP.H4 > 0.80). PheWAS showed no genome-wide liabilities for either gene. Regional expression suggested white-matter enrichment for BTBD16 and a cerebellar peak for RIMS1.

Conclusions: Cell-type-specific MR sharpens migraine mechanisms beyond bulk tissue and prioritizes inhibitory-neuronal BTBD16 (protective) and astrocytic RIMS1 (risk-increasing) for mechanistic validation and therapeutic exploration.

Background: Suicide is considered as common in patients with cluster headache (CH) and is defined as 'suicidal headache'. However, the exact level of suicidality is not known and is intuitively assumed to be correlated with the CH severity.

Methods: This work is a systematic review of data accessible through PubMed and published up to July 25, focusing on the suicidality of CH according to the rates of suicidal ideation and suicide attempts. This meta-analysis was carried out with all selected studies then by considering studies with specialized recruitment and studies with non-specialized recruitment. A qualitative analysis was performed to identify determinants of CH suicidality.

Results: Among the 53 publications identified, 12 were selected corresponding to 10 studies. These selected studies included a total of 34180 subjects (range 75-24131). Eight were performed in a specialized field (headache tertiary center, neurology clinic or via CH patients' association) and 2 in a non-specialized field (via heath registry). The overall rate of suicidal ideation in CH was estimated at 8.0% (95%CI [7.7; 8.3] and overall rate of suicide attempts in CH was estimated at 1.2% (95%CI [1.1; 1.3]). In a non-specialized field, these rates were estimated at 5.2% (95%CI [4.9; 5.4]) and 1.1% (95%CI [1.0; 1.2]) respectively. In specialized field, these rates were estimated at 44.6% (95%CI [42.7; 46.6]) and 5.1% (95%CI [3.9; 6.7]) respectively. The qualitative analysis showed that few determinants have been considered but it appears that the risk is greater during CH attacks, and it involves psychological determinants such as demoralization.

Conclusion: The overall suicidal risk in CH does not appear to be higher than that of the general population, but there is a suicidal risk increase among CH patients followed up in specialized field. This higher risk is indeed probably related to the severity of CH in terms of pain, but it is also probably related to other factors such as impulsive aggressiveness during CH attacks and psychological factors such as demoralization.

Registration: The systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 07/22/2025 (number: CRD420251110095).

Background: The Global Campaign against Headache is undertaking a worldwide programme of cross-sectional schools-based studies of headache prevalence and attributed burden among children (6-11 years) and adolescents (12-17). The purpose is to expand the still sparse knowledge of headache among these age groups, using a data-acquisition technique that cluster-samples the world. This survey in Georgia was the fourth in the European Region, following similar studies in Turkey, Austria and Lithuania, and others in African, Eastern Mediterranean, South-East Asia and Western Pacific Regions.

Methods: We used the Global Campaign's standardized protocol, selecting schools representative of the country. The child and adolescent versions of the structured HARDSHIP questionnaire, translated into Georgian language, were completed by pupils under supervision in class. Headache diagnoses followed ICHD-3, with the exception of undifferentiated headache (UdH), which we defined initially as mild and subsequently as mild-to-moderate headache lasting < 1 h. Enquiry timeframes were 1 year, 4 weeks and 1 day (headache yesterday [HY]).

Results: Of 2,790 participants, two thirds (68.5%) reported headache in the preceding year (age- and gender-adjusted 1-year prevalence: 66.3%). HY was reported by 20.4%, a proportion that might be expected to have headache on any day. Headache on ≥ 15 days/month (H15+) was common (4.1%), with probable medication-overuse headache (pMOH) accounting for 0.5% (0.2% among children, 0.7% among adolescents; p = 0.06). UdH took diagnostic precedence over migraine and tension-type headache (TTH), so all other estimates were influenced by the definition of UdH. By the conventional (initial) definition, 1-year prevalence of UdH was 18.2%; by the modified definition, it was 30.2%. Estimates for migraine and TTH, 29.1% and 13.1% respectively with UdH defined conventionally, were reduced to 22.2% and 9.5% with the modified definition.

Conclusions: Headache is very common among children and adolescents in Georgia. The findings raise particular concern about the prevalence of H15 + in young people, with a strong trend of increasing pMOH with age. They also highlight the diagnostic uncertainties inherent in epidemiological studies in these age groups. With the definition of UdH a dominating issue, the findings support the view that it needs to be modified, without offering a definitive solution.

Migraine with aura is a phenotypically heterogeneous disorder characterized by scintillating scotoma, sensory, language, and/or motor disturbance often followed by a severe headache, and cutaneous allodynia. Cortical spreading depression (SD), a neuro-glial slowly propagating depolarizing wave, is the likely electrical event responsible for aura and a headache trigger. While clinical and preclinical observations support these relationships, there remains controversy over the role of SD as a model of migraine. This article as part of a series of debate articles will focus on data supporting SD as a model of migraine given the relationship of SD to migraine with aura, the evidence for SD as a trigger for trigeminal pain and SD and its downstream events as targets for migraine therapeutic intervention. Taken together, the bounty of evidence suggests SD has face, construct and predictive validity for migraine and can be used as a robust and reliable model of migraine with aura.

Background: Social exclusion, whether due to physical isolation or the subjective perception of being ignored and unwanted, threatens the fundamental human need for social belonging and is experienced as social pain. While its detrimental effects on mood disorders are well documented, its impact on individuals living with chronic pain remains largely unexplored. This study investigates emotional responses to social exclusion in individuals with chronic pain (CPs) compared to healthy controls (HCs), considering the role of comorbid mood disturbances. It also examines whether behavioral and social functioning, across cognitive and psychological domains, modulate the experience and impact of social exclusion.

Methods: We recruited 38 CPs and 38 HCs, grouped according to validated cut-offs on the Hospital Anxiety and Depression Scale as follow: 22 Normal-CPs (G1), 16 Altered-CPs (G2), 22 Normal-HCs (G3) and 16 Altered-HCs (G4). All participants completed the Cyberball task, a virtual ball-tossing game designed to simulate social inclusion (control condition) and exclusion (ostracism condition) by manipulating the distribution of ball tosses. After each condition, participants reported their mood, emotional state, and perceived threat to psychological needs. Additional assessments included pain intensity, coping strategies, social functioning, and social cognition.

Results: All groups were matched for age, sex, education, and cognitive efficiency. Participants with mood alterations (G2 and G4) reported higher levels of loneliness than the other groups. All CPs showed higher levels of catastrophizing compared to HCs. In the Cyberball task, all participants felt more excluded in the exclusion condition than in the inclusion condition, indicating decreased well-being following ostracism. Notably, only Altered-CPs exhibited blunted emotional reactivity after exclusion. Compared to HCs, Altered-CPs reported lower self-esteem, reduced happiness, and greater negative affect even during the inclusion condition. Correlation analyses revealed that psychological responses to social exclusion in CPs were associated with mood symptoms, catastrophizing, loneliness, and perceived social isolation.

Conclusion: These findings suggest that chronic pain, particularly when accompanied by mood disorders, alters emotional processing and increases sensitivity to social context, even in neutral or positive social situations. Addressing social functioning may be crucial for developing personalized and effective treatment strategies for chronic pain.