Background

Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine.

Methods

The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components.

Results

Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake.

Conclusion

The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.

clinicaltrials.gov NTC04324710.

中文翻译：

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发作性和慢性偏头痛患者的内源性大麻素系统成分的外周变化：一项初步研究。

背景

临床前和临床证据表明，内源性大麻素系统失调在偏头痛中起作用，尤其是在慢性偏头痛患者中。

方法

在 25 名发作性偏头痛受试者、26 名慢性偏头痛伴药物过度使用 (CM-MO) 受试者和 24 名年龄匹配的健康对照者的外周血单核细胞中检测了内源性大麻素系统成分的基因表达。我们还评估了大麻素受体 1 和 2 的蛋白质表达以及参与内源性大麻素系统成分的基因的 DNA 甲基化变化。

结果

与对照组相比，发作性偏头痛和 CM-MO 受试者均显示出更高的大麻素受体 1 和大麻素受体 2 基因和蛋白质表达。与健康对照受试者相比，偏头痛组中参与花生四烯酸降解的脂肪酸酰胺水解酶基因表达较低。N-花生四烯酰磷脂酰乙醇胺磷脂酶 D 基因表达在所有偏头痛患者中均显着升高，单酰基甘油脂肪酶和二酰基甘油脂肪酶基因表达也是如此。上述标志物与偏头痛天数和急性药物摄入天数显着相关。

结论

研究结果指出偏头痛患者中发生的内源性大麻素系统成分的转录变化。这些变化是在外围检测到的，这使得它们能够被更广泛地采用，以进一步研究它们在临床领域中的作用和适用性。

Clinicaltrials.gov NTC04324710。