Journal of Headache and Pain最新文献

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.

Background: To assess the efficacy of psychological interventions for Tension-Type Headache (TTH) via a systematic review and meta-analysis.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to June 2025 for randomized controlled trials (RCTs) comparing psychological interventions with controls in patients with TTH. The primary outcome was the number of headache days per month, while secondary outcomes were headache intensity and the treatment response rate. The second version of the Cochrane Risk-of-Bias Tool (RoB 2.0) was used to assess the risk of bias, and GRADE was used to assess the quality of evidence.

Results: Nineteen studies with 1069 participants were included. For the primary outcome, psychological interventions reduced the number of headache days per month compared to controls (5 studies, MD=-4.53, 95% CI: -5.52 to -3.54, p < 0.01, I² = 35%), with moderate-quality evidence. For secondary outcomes, the treatment response rate was higher in the intervention group (7 studies, RR = 2.43, 95% CI: 1.32 to 4.48, p < 0.01, I²=41%). Psychological interventions also decreased headache intensity compared to controls (10 studies, MD=-1.88, 95% CI: -2.72 to -1.04, p < 0.01, I²=93%). Subgroup analysis of headache intensity indicated significant differences between interventions (P = 0.01), suggesting effect heterogeneity across psychological modalities.

Conclusions: Psychological interventions effectively reduce the number of headache days, headache intensity, and improve response rates in TTH. Psychological interventions are an effective non-pharmacological approach for managing TTH, although heterogeneity in some outcomes warrants further high quality trials.

Background: Migraine is a highly disabling neurovascular disorder, yet its underlying molecular mechanisms remain incompletely understood. Emerging evidence implicates epigenetic modifications, particularly DNA methylation, in migraine pathophysiology, but whether these changes play a causal role has not been established.

Methods: We integrated large-scale brain and blood methylation quantitative trait loci (mQTL) datasets with genome-wide association study (GWAS) data to investigate the causal role of DNA methylation in migraine and its subtypes. Two-sample Mendelian randomization (MR) was applied to evaluate the effects of cytosine-phosphate-guanine (CpG) methylation on migraine risk. Significant CpG sites were annotated to genes and refined through a multi-step prioritization framework incorporating colocalization, expression QTL (eQTL)-MR, two-step MR, and gene-based association analyses. Functional enrichment, protein-protein interaction, and drug-gene analyses were then performed to explore biological mechanisms and therapeutic potential.

Results: We identified 169 CpG sites with causal effects on migraine, mapping to 68 genes. Subtype analyses revealed 10 additional genes associated with MA and MO, including three genes specific to MA and one to MO, expanding the total to 72 non-overlapping migraine risk genes. Integrative prioritization highlighted 12 high-confidence genes, among which CFDP1, ICA1L and SERPING1 was supported by all five analytical approaches. Functional characterization indicated significant enrichment in calcitonin-like ligand receptors, axon development and neurovascular regulation, while drug-gene interaction analyses suggested therapeutic potential for targets such as MAPT and CALCA.

Conclusion: Our findings provide robust evidence that DNA methylation contributes causally to migraine risk and its subtypes, identify genes of biological and therapeutic relevance, and offer novel insights into the epigenetic mechanisms underlying migraine pathophysiology.