Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet th...Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.展开更多
目的分析中国1990—2021年紧张性头痛的疾病负担现状与变化趋势,确定重点防控人群,并预测2022—2035年的变化趋势,为制定紧张性头痛的防治措施提供依据。方法基于2021年全球疾病负担研究(Global Burden of Disease Study 2021,GBD 2021...目的分析中国1990—2021年紧张性头痛的疾病负担现状与变化趋势,确定重点防控人群,并预测2022—2035年的变化趋势,为制定紧张性头痛的防治措施提供依据。方法基于2021年全球疾病负担研究(Global Burden of Disease Study 2021,GBD 2021)数据库,获取1990—2021年中国紧张性头痛的疾病负担数据,包括发病率、患病率、伤残调整寿命年(disability-adjusted life year,DALY)等指标。利用Joinpoint回归模型分析紧张性头痛疾病负担的变化趋势,并采用贝叶斯年龄-时期-队列(Bayesian age-period-cohort,BAPC)模型按年龄、性别分层对中国紧张性头痛的疾病负担进行评估。结果1990—2021年中国紧张性头痛的发病数、患病数和DALY增幅分别为32.61%、39.08%、46.32%,均呈上升趋势。男性与女性的发病率和患病率在30~34岁和70~74岁年龄组分别出现上升拐点,呈现双峰分布,并在≥95岁年龄组达到峰值;DALY率在40~44岁年龄段达到峰值。1990—2021年女性DALY、发病率和患病率均高于男性。预计2022—2035年,中国居民的紧张性头痛发病率、患病率和DALY率将持续上升,但整体波动幅度较小。结论1990—2021年中国紧张性头痛的疾病负担上升,预计至2035年,中国居民的紧张性头痛疾病负担将持续加重,应采取全面预防措施,重点关注女性群体,并建立有效的防控体系。展开更多
基金supported by the National Natural Science Foundation of China(No.32571336 and 32271048)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(No.2025IHM01100)。
文摘Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.
文摘目的分析中国1990—2021年紧张性头痛的疾病负担现状与变化趋势,确定重点防控人群,并预测2022—2035年的变化趋势,为制定紧张性头痛的防治措施提供依据。方法基于2021年全球疾病负担研究(Global Burden of Disease Study 2021,GBD 2021)数据库,获取1990—2021年中国紧张性头痛的疾病负担数据,包括发病率、患病率、伤残调整寿命年(disability-adjusted life year,DALY)等指标。利用Joinpoint回归模型分析紧张性头痛疾病负担的变化趋势,并采用贝叶斯年龄-时期-队列(Bayesian age-period-cohort,BAPC)模型按年龄、性别分层对中国紧张性头痛的疾病负担进行评估。结果1990—2021年中国紧张性头痛的发病数、患病数和DALY增幅分别为32.61%、39.08%、46.32%,均呈上升趋势。男性与女性的发病率和患病率在30~34岁和70~74岁年龄组分别出现上升拐点,呈现双峰分布,并在≥95岁年龄组达到峰值;DALY率在40~44岁年龄段达到峰值。1990—2021年女性DALY、发病率和患病率均高于男性。预计2022—2035年,中国居民的紧张性头痛发病率、患病率和DALY率将持续上升,但整体波动幅度较小。结论1990—2021年中国紧张性头痛的疾病负担上升,预计至2035年,中国居民的紧张性头痛疾病负担将持续加重,应采取全面预防措施,重点关注女性群体,并建立有效的防控体系。
