偏头痛是most common brain disorder in people aged under 50 years. Migraine attacks occur with external and internal triggers in susceptible individuals. Migraine food triggers such as chocolate, cheese, wine, and citrus fruits are well known, but it is still a mystery how they start a migraine attack. It is also unclear why food triggers do not always cause headaches and why there are certain episodes when migraine patients are more prone to food triggers.
Certain ingredients in these food triggers inhibit a group of enzymes known as sulfotransferases (SULT) which are involved in the detoxification of drugs and chemicals and the metabolism of neurotransmitters and hormones. For example, quercetin and catechin in chocolate, hesperidin in orange and lemon, quinic and caffeic acids in coffee, and epicatechin gallate in tea and red wine inhibit SULT1A1 enzymes.
Migraine attacks are usually treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and the overuse of analgesics transforms migraine into chronic migraine, which is defined as having headaches on more than 15 days per month. Surprisingly, NSAIDs have also been shown to inhibit SULT1A1 enzymes. The mechanism underlying the link between medication overuse and the transformation of migraine is unknown.
We hypothesized that sulfotransferase inhibition was the common mechanism by which food triggers and analgesics synergistically affect migraine susceptibility. Medication overuse by inhibiting these enzymes could make migraine patients more susceptible to triggers, and food triggers even in low amounts could result in chronic headache with exacerbations.
因此，我们通过向大鼠施用甲氟酸4周来开发出一种过度使用头痛模型。我们还从柑橘类水果中使用了紫杉醇。使用微电极记录脑波和皮质扩散抑郁症（CSD），以评估皮质兴奋性和偏头痛的敏感性。还评估了与偏头痛和焦虑行为相关的疼痛行为。在实验结束时，收集了脑样品，并测量了Sult1a1酶活性。
我们首次证明了慢性甲氟酸会显着降低CSD阈值，增加CSD频率，引起机械性热超敏反应，诱发疼痛焦虑样行为并抑制SULT1A1酶活性。硫糖蛋白和慢性甲氟酸的暴露共同增加了CSD的敏感性和与Sult1A1抑制相关的疼痛行为，尽管单独单剂量硫代素并未显示出任何显着作用。
Our research showed inhibition of sulfotransferase enzyme activity as a new mechanism by which analgesic overuse transforms migraine into chronic migraine. We also showed that migraine food triggers via SULT1A1 inhibition may further increase migraine attacks in chronic migraine patients with medication overuse. Chronic analgesic use increases CSD susceptibility and could make the brain more susceptible to the effects of migraine triggers. Under these circumstances, even subthreshold triggers that cannot initiate a migraine attack alone may initiate a migraine attack.
We believe SULT1A1 inhibition is a common mechanism by which medication overuse and migraine triggers affect migraine susceptibility, which may provide a new potential treatment target.
注释