偏头痛与中枢敏化陈春富

偏头痛与中枢敏化陈春富山东省立医院神经内科AminFM,AsgharMS,HougaardA,etal.Magneticresonanceangiographyofintracranialandextracranialarteriesinpatientswithspontaneousmigrainewithoutaura:across-sectionalstudy.LancetNeurol,2019;12(5):454-61.偏头痛，不是血管扩张惹的祸荷兰学者研究发现，偏头痛发作时并不存在颅外动脉扩张，仅有轻度的颅内动脉扩张。提示未来有关偏头痛的研究应关注于外周和中枢性疼痛通路而非单纯的动脉扩张。概念1983年Woolf首次提出外伤后疼痛的中枢敏感化的概念，用来描述中枢神经系统在生理或解剖上任何增强基底敏感性、疼痛感知、神经兴奋性的变化。头痛：因重复或长时间的疼痛刺激，外周炎症或神经受损，使中枢神经系统的痛觉通路尤其是三叉神经尾核、脊髓背角感觉神经元等产生一种长期的可逆的兴奋性增高，兴奋阈值降低，突触效能增加的现象。WoolfCJ.Evidenceforacentralcomponentofpost-injurypainhypersensitivity.Nature,1983;306:686-8.AguggiaM.Allodyniaandmigraine.NeurolSci,2019;33(Suppl1):S9-11中枢敏化综合征Fibro-myalgiasyndromeMPSTMDRestlesslegssyndromePLMDMCSPTSDDepressionPrimarydysmenorrheamigraineT-TheadacheIBSCFSCentralSensitization偏头痛与中枢敏化1832年，头痛伴发头皮压痛被首次报道。2019年Burstein等在第九届世界疼痛大会首次报道了偏头痛患者存在中枢敏感化现象，随后相关研究相继证实了这一发现。BursteinR,Goor-AryehI,YamitskyD,etal.Cutaneousallodyniaduringmigraine:anewneurologicalfindingandanewinsightintothepathophysiology.ProgramandabstractsoftheNinthWorldCongressonPain;August22-27,2019;Vienna,AustriaAfridiSK,etal.Brain,2019,128:932-939;偏头痛在头痛的同侧脑干功能激活偏头痛患者下丘脑功能的激活Denuelleetal.Headache,2019偏头痛患者出现脑体积减少的区域偏头痛患者可出现疼痛的下行调制系统中灰质密度或体积的减少：扣带回皮质岛叶前额叶皮质杏仁核顶叶皮质颞上回和颞极ValfrèWetal.Headache,2019;48(1):109-117.RoccaMAetal.Stroke,2019;37(7):1765-1770.KimJHetal.Cephalalgia,2019;28(6):598-604.中枢敏化的表现痛觉过敏：轻微疼痛刺激即感到疼痛难忍异常性疼痛：非疼痛性刺激引起痛觉感受疼痛感知区域大于疼痛刺激区域在极短的伤害性刺激后出现持续的疼痛感觉自发性疼痛TuchmanM,BarrettJA,DonevanS,etal.CentralsensitizationandCa(V)α2δligandsinchronicpainsyndromes:pathologicprocessesandpharmacologiceffect.JPain.2019;11(12):1241-1249NinanT.Mathew,MD.Pathophysiologyofchronicmigraineandmodeofactionofpreventivemedications.Headache.2019;51(Suppl2):84-92.BigalME,AshinaS,BurnsteinR,etal.Prevalenceandcharacteristicofallodyniainheadachesufferers:apopulationstudy.Neurology.2019;70(17):1525–1533偏头痛–伴有广泛的感觉敏感性提高的脑功能状态先兆语言症状运动功能障碍打哈欠,尿意自发性神经化学改变感觉症状视觉症状头晕眩晕皮肤痛敏头痛对光、声、气味敏感恶心呕吐疲乏情绪改变认知功能失调偏头痛CA部位Clinicalpresentationofcephalicandextracephalicallodyniaduringmigraine.Numberdepictpainintensity,coldpainthreshold,heatpainthresholdandmechanicalpainthreshold.Areasshadedingreenindicatevaluesconsideredasallodynic.CL:contralateral,IL:ipsilateral,VFH:von-frayhair.Brain,2000,123:1703-1709偏头痛频率、病程与CACalandreEP,etal.Triggerpointevaluationinmigrainepatients.EurJNeurol,2019,13:244–9偏头痛程度与CALiuB,etal.AnalysisoftheDevelopmentofAllodynia:CorrelationBetweenMigraineDurationandSeverity.StudyfundedbyMAPPharmaceuticals,Inc.2019CA与诱发因素中重度CA的患者具有更多的诱发因素（OR=2.8）（诱发因素7）BaldacciF,etal.Triggersinallodynicandnon-allodynicmigraineurs.Aclinicsettingstudy.Headache,2019;53(1):152-60.CA与偏头痛CA是中枢敏感化的一个标志1CA是偏头痛慢性化的一个危险因素21.LouterMA,etal.Brain,2019;136(Pt11):3489-96.2.BigalME,etal.Neurology,2019;70(17):1525–1533偏头痛与RLS24项研究荟萃：偏头痛患者RLS发生率8.7%～39.0%，不受性别、先兆的影响RLS患者偏头痛发生率15.1%～62.6%缺陷：其他类型头痛RLS情况？47%的不宁腿综合症患者有头痛家族史SchürksM,etal.Migraineandrestlesslegssyndrome:Asystematicreview.Cephalalgia,2019;34(10):777-94.偏头痛与RLS慢性偏头痛RLS发生率34.3%，发作性偏头痛组16%（P=0.0006)RLS患者偏头痛MIDAS评分高28.5%的偏头痛患者有RLS家族史LucchesiC,etEvidenceofincreasedrestlesslegssyndromeoccurrenceinchronicandhighlydisablingmigraine.FunctionalNeurology,2019;27(2):91-94偏头痛与抑郁偏头痛OR=2.35～3.22除了偏头痛发作频率外，CA列第二位BreslauN,DavisGC.Migrainephysicalhealthandpsychiatricdisorder:aprospectiveepidemiologicstudyinyoungadults.JPsychiatrRes,1993,27:211-221.LouterM1,WardenaarK,VeenG,etal.Allodyniaisassociatedwithahigherprevalenceofdepressioninmigrainepatients.Cephalalgia,2019[Epubaheadofprint]BreslauN,SchultzLR,StewartAT,etal.Headacheandmajordepression:istheassociationspecifictomigraine?Neurology,2000,54:308-313.抑郁与偏头痛OR=1.52,95%CI1.26-1.841OR=1.22inmilddepression(95%CI1.10to1.35)OR=1.62inseveredepression(95%CI1.34to1.96).21.LouterMA1,etal.Brain,2019;136(Pt11):3489-96.2.BigalME,etal.Prevalenceandcharacteristicsofallodyniainheadachesufferers:apopulationstudy.Neurology,2019;70(17):1525-33.FMS与偏头痛22.2%女性偏头痛患者伴发FMS131.4%偏头痛患者伴发FMS，与先兆无关235%-88%FMS伴发头痛3，伴发偏头痛63%,MOH8%41.IferganeG,etal.Prevalenceoffibromyalgiasyndromeinmigrainepatients.Cephalalgia,2019;26(4):451-6.2.KüçükşenS,Theprevalenceoffibromyalgiaanditsrelationwithheadachecharacteristicsinepisodicmigraine.ClinRheumatol,2019;32(7):983-90.3.ValençaMM,etal.Neuroendocrinedysfunctioninfibromyalgiaandmigraine.CurrPainHeadacheRep.2009;13(5):358-64.4.MarcusDA,etal.Fibromyalgiaandheadache:anepidemiologicalstudysupportingmigraineaspartofthefibromyalgiasyndrome.ClinRheumatol,2019;24(6):595-601.FMS与偏头痛5-HT异常1兴奋性氨基酸异常2下丘脑、脑干疼痛加工机制异常31.NicolodiM1,SicuteriF.Fibromyalgiaandmigraine,twofacesofthesamemechanism.Serotoninasthecommonclueforpathogenesisandtherapy.AdvExpMedBiol,2019;398:373-9.2.DiFilippoM,etal.SarchielliP,Sensitization,glutamate,andthelinkbetweenmigraineandfibromyalgia.CurrPainHeadacheRep,2019;11(5):343-51.3.ValençaMM,etal.Neuroendocrinedysfunctioninfibromyalgiaandmigraine.CurrPainHeadacheRep.2009;13(5):358-64.TMD与偏头痛85.5%TMD伴头痛，偏头痛55.3%（OR=2.76(95%CI1.50-5.06)1偏头痛发作频率与TMD疼痛程度正相关154%偏头痛咀嚼肌压痛(OR=3.0,95%CI1.1-8.9)。CM=73%(OR=6.9,9