Foundation Allineare Sanità and Salute, Scientific Committee, Milan, Italy; LUMEN APS, European Salus Network, Scientific Committee, San Pietro in Cerro (PC), Italy.
Neurology Unit, ASL AL, San Giacomo Hospital, Novi Ligure, Italy.
J Pain. 2022 Aug;23(8):1294-1317. doi: 10.1016/j.jpain.2022.02.006. Epub 2022 Mar 14.
Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance. This condition has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis, mainly during high metabolic demand. This scoping review examines the clinical, epidemiologic and pathophysiologic data supporting the hypothesis that abnormalities in brain glucose metabolism may generate a mismatch between the brain's energy reserve and metabolic expenditure, triggering migraine attacks. Moreover, alteration in glucose homeostasis could generate a chronic brain energy deficit promoting migraine chronification. Lastly, insulin resistance may link migraine with its comorbidities, like obesity, depression, cognitive impairment and cerebrovascular diseases. PERSPECTIVE: Although additional experimental studies are needed to support this novel "neuroenergetic" hypothesis, brain insulin resistance in migraineurs may unravel the pathophysiological mechanisms of the disease, explaining the migraine chronification and connecting migraine with comorbidities. Therefore, this hypothesis could elucidate novel potential approaches for migraine treatment.
越来越多的证据表明，偏头痛可能是大脑葡萄糖代谢受损的结果。一些研究报告称，偏头痛患者的大脑线粒体功能障碍、大脑葡萄糖代谢受损和特定脑区灰质体积减少。此外，在几项研究中已经证明的外周胰岛素抵抗可能会延伸到大脑，导致大脑胰岛素抵抗。这种情况已被证明会下调星形胶质细胞和神经元中的胰岛素受体，从而减少葡萄糖摄取和糖原合成，主要发生在高代谢需求期间。这项范围综述检查了支持以下假设的临床、流行病学和病理生理学数据：大脑葡萄糖代谢异常可能导致大脑能量储备和代谢消耗之间不匹配，从而引发偏头痛发作。此外，葡萄糖稳态的改变可能会导致慢性大脑能量不足，从而促进偏头痛的慢性化。最后，胰岛素抵抗可能将偏头痛与其共病（如肥胖、抑郁、认知障碍和脑血管疾病）联系起来。观点：尽管需要更多的实验研究来支持这一新颖的“神经能量”假说，但偏头痛患者的大脑胰岛素抵抗可能会揭示疾病的病理生理学机制，解释偏头痛的慢性化，并将偏头痛与共病联系起来。因此，这一假说可以阐明偏头痛治疗的新潜在方法。
