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Migraine is a pain disorder accompanied by various symptoms. The insula, a "cortical hub," is involved in many functions. Few studies have focused on the insula in migraine. We explored the resting-state functional connectivity between the insula and other brain areas in rats subjected to repeated meningeal nociception which was commonly used as animal model of migraine. Inflammatory soup was infused through supradural catheters in conscious rats. The rats were subdivided based on the frequency of the inflammatory soup infusions. Magnetic resonance imaging data were acquired on rats 21 days after inflammatory soup infusion and functional connectivity seeded on the insula was analyzed. In the low-frequency inflammatory soup group, magnetic resonance imaging was performed again 1 h after the glyceryl trinitrate injection following baseline scanning. The cerebellum showed increased functional connectivity with the insula in the inflammatory soup groups. The insula showed increased functional connectivity with the medulla and thalamus in the ictal period in the low-frequency inflammatory soup rats. In the high-frequency inflammatory soup group, several areas showed increased functional connectivity with the insula, including the pons, midbrain, thalamus, temporal association cortex, and retrosplenial, visual, and sensory cortices. Our findings support the hypothesis that the headache phase of migraine depends on the activation and sensitization of the trigeminovascular system, and that the chronification of migraine may be related to higher brain centers and limbic cortices. The insula may be a new target for treatment of migraine. [ABSTRACT FROM AUTHOR]

Background: Cluster headache (CH), a rare primary headache disorder, is currently thought to be a genetic susceptibility which play a role in CH susceptibility. A large numbers of genetic association studies have confirmed that the HCRTR2 (Hypocretin Receptor 2) SNP rs2653349, and the ADH4 (Alcohol Dehydrogenase 4) SNP rs1126671 and rs1800759 polymorphisms are linked to CH. In addition, the CLOCK (Circadian Locomotor Output Cycles Kaput) gene is becoming a research hotspot for CH due to encoding a transcription factor that serves as a basic driving force for circadian rhythm in humans. The purpose of this study was to evaluate the association between CH and the HCRTR2, ADH4 and CLOCK genes in a Chinese CH case-control sample. Methods: We genotyped polymorphisms of nine single nucleotide polymorphisms (SNPs) in the HCRTR2, ADH4 and CLOCK genes to perform an association study on a Chinese Han CH case-control sample (112 patients and 192 controls),using Sequenom MALDI-TOF mass spectrometry iPLEX platform. The frequencies and distributions of genotypes and haplotypes were statistically compared between the case and control groups to identify associations with CH. The effects of SNPs on CH were further investigated by multiple logistic regression. Results: The frequency of the HCRTR2 SNP rs3800539 GA genotype was significantly higher in cases than in controls (48.2% vs.37.0%). The GA genotypes was associated with a higher CH risk (OR = 1.483, 95% CI: 0.564-3.387, p = 0.038), however, after Bonferroni correction, the association lost statistical significance. Haplotype analysis of the HCRTR2 SNPs showed that among eight haplotypes, only H1-GTGGGG was linked to a reduced CH risk (44.7% vs. 53.1%, OR = 0.689, 95% CI =0.491~0.966, p = 0.030). No significant association of ADH4, CLOCK SNPs with CH was statistically detected in the present study. Conclusions: Association between HCRTR2, ADH4,CLOCK gene polymorphisms and CH was not significant in the present study, however, haplotype analysis indicated H1-GTGGGG was linked to a reduced CH risk. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. Methods: Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. Results: In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. Conclusion: Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine. [ABSTRACT FROM AUTHOR]