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
文摘目的:研究针刺对急性偏头痛患者血浆中降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、一氧化氮合酶(nitric oxide synthase,NOS)表达的影响及临床疗效评价。方法:选取2023年3月―2024年3月就诊于银川市第一人民医院中医科门诊及住院的急性偏头痛患者作为研究对象,采用随机数生成器将60例急性期偏头痛患者分为单穴组(30例)、腧穴配伍组(30例),单穴组选择针刺风池穴治疗,腧穴配伍组选择风池穴、率谷穴、外关穴、合谷穴、太冲穴、后溪穴,每日针刺治疗1次,每次30分钟,连续治疗5天,每周休息2天,7天为一个疗程,共治疗4个疗程,比较两组治疗4周后头痛发作的次数、疼痛视觉模拟评分法(visual analogue scale,VAS)评分、总有效率、偏头痛特异性生活品质问卷(migraine specific quality of life questionnaire,MSQ),以及患者血浆中CGRP及NOS表达。结果:①头痛发作频率:两组治疗后头痛发作频率均较治疗前明显减少(P<0.01),差异具有统计学意义;②VAS评分:两组VAS评分均较治疗前明显下降,具有显著差异性(均P<0.01);③总有效率:腧穴配伍组明显改善24例,稍有改善6例;单穴组明显改善20例,稍有改善9例,无效1例。④MSQ评分:在针刺治疗后,两组患者功能受限、功能障碍、情感障碍领域明显改善,且腧穴配伍组优于单穴组。⑤CGRP及NOS表达:两组患者血浆中CGRP及NOS水平均较治疗前降低(P<0.01),但组间差异无统计学意义。结论:针刺疗法可显著降低偏头痛发作频率及VAS评分,改善患者生活质量,整体效果优于单穴,但在降低NOS及CGRP水平方面与单穴组的差异无统计学意义;腧穴配伍发挥协同效应,具有多靶点、多途径的优势;单穴也有最佳效应,但二者存在效应差异。
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.
