偏头痛与中枢敏化--陈春富.ppt

陈春富 山东省立医院神经内科山东省立医院神经内科 Amin FM,Asghar MS,Hougaard A,et al.Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura:a cross-sectional study.Lancet Neurol,2013;12(5):454-61.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。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。Woolf CJ.Evidence for a central component of post-injury pain hypersensitivity.Nature,1983;306:686-8.Aguggia M.Allodynia and migraine.Neurol Sci,2012;33(Suppl 1):S9-11 1832年，头痛伴发头皮压痛被首次报道。1999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。Burstein R,Goor-Aryeh I,Yamitsky D,et al.Cutaneous allodynia during migraine:a new neurological finding and a new insight into the pathophysiology.Program and abstracts of the Ninth World Congress on Pain;August 22-27,1999;Vienna,Austria Afridi SK,et al.Brain,2005,128:932-939;偏头痛患者下丘脑功能的激活偏头痛患者下丘脑功能的激活 Denuelle et al.Headache,2007 偏头痛患者可出现疼痛的下行调制偏头痛患者可出现疼痛的下行调制系统中灰质密度或系统中灰质密度或体积的减少体积的减少：扣带回皮质扣带回皮质 岛叶岛叶 前额叶皮质前额叶皮质 杏仁核杏仁核 顶叶皮质顶叶皮质 颞上回和颞极颞上回和颞极 Valfr W et al.Headache,2008;48(1):109-117.Rocca MA et al.Stroke,2006;37(7):1765-1770.Kim JH et al.Cephalalgia,2008;28(6):598-604.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 Tuchman M,Barrett JA,Donevan S,et al.Central sensitization and Ca(V)2 ligands in chronic pain syndromes:pathologic processes and pharmacologic effect.J Pain.2010;11(12):1241-1249 Ninan T.Mathew,MD.Pathophysiology of chronic migraine and mode of action of preventive medications.Headache.2011;51(Suppl 2):84-92.Bigal ME,Ashina S,Burnstein R,et al.Prevalence and characteristic of allodynia in headache sufferers:a population study.Neurology.2008;70(17):15251533 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 皮肤痛敏皮肤痛敏 头 痛 对光、声、气味对光、声、气味 敏感敏感 恶心恶心 呕吐呕吐 疲乏 情绪改变 认知功能失调 Clinical presentation of cephalic and extracephalic allodynia during migraine.Number depict pain intensity,cold pain threshold,heat pain threshold and mechanical pain threshold.Areas shaded in green indicate values considered as allodynic.CL:contralateral,IL:ipsilateral,VFH:von-fray hair.Brain,2000,123:1703-1709 Calandre EP,et al.Trigger point evaluation in migraine patients.Eur J Neurol,2006,13:2449 Liu B,et al.Analysis of the Development of Allodynia:Correlation Between Migraine Duration and Severity.Study funded by MAP Pharmaceuticals,Inc.2012 中重度CA的患者具有更多的诱发因素（OR=2.8）（诱发因素7）Baldacci F,et al.Triggers in allodynic and non-allodynic migraineurs.A clinic setting study.Headache,2013;53(1):152-60.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 2 1.Louter MA,et al.Brain,2013;136(Pt 11):3489-96.2.Bigal ME,et al.Neurology,2008;70(17):15251533 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 Sch rks M,et al.Migraine and restless legs syndrome:A systematic review.Cephalalgia,2014;34(10):777-94.慢性偏头痛慢性偏头痛RLS发生率34.3%34.3%，发作性偏头痛组，发作性偏头痛组16%16%（P=0.0006)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 Lucchesi C,et Evidence of increased restless legs syndrome occurrence in chronic and highly disabling migraine.Functional Neurology,2012;27(2):91-94 偏头痛 OR=2.353.22 除了偏头痛发作频率外，CA列第二位 Breslau N,Davis GC.Migraine physical health and psychiatric disorder:a prospective epidemiologic study i n young adults.J Psychiatr Res,1 993,27:211-221.Louter M1,Wardenaar K,Veen G,et al.Allodynia is associated with a higher prevalence of depression in migraine patients.Cephalalgia,2014Epub ahead of print Breslau N,Schultz L R,Stewart AT,et al.Headache and major depression:is the association specific to migraine?Neurology,2000,54:308-313.OR=1.52,95%CI 1.26-1.841 OR=1.22 in mild depression(95%CI 1.10 to 1.35)OR=1.62 in severe depression(95%CI 1.34 to 1.96).2 1.Louter MA1,et al.Brain,2013;136(Pt 11):3489-96.2.Bigal ME,et al.Prevalence and characteristics of allodynia in headache sufferers:a population study.Neurology,2008;70(17):1525-33.22.2%女性偏头痛患者伴发FMS 1 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%,MOH 8%4 1.Ifergane G,et al.Prevalence of fibromyalgia syndrome in migraine patients.Cephalalgia,2006;26(4):451-6.2.Kken S,The prevalence of fibromyalgia and its relation with headache characteristics in episodic migraine.Clin Rheumatol,2013;32(7):983-90.3.Valen a MM,et al.Neuroendocrine dysfunction in fibromyalgia and migraine.Curr Pain Headache Rep.2009;13(5):358-64.4.Marcus DA,et al.Fibromyalgia and headache:an epidemiological study supporting migraine as part of the fibromyalgia syndrome.Clin Rheumatol,2005;24(6):595-601.5-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 3 1.Nicolodi M1,Sicuteri F.Fibromyalgia and migraine,two faces of the same mechanism.Serotonin as the common clue for pathogenesis and therapy.Adv Exp Med Biol,1996;398:373-9.2.Di Filippo M,et al.Sarchielli P,Sensitization,glutamate,and the link between migraine and fibromyalgia.Curr Pain Headache Rep,2007;11(5):343-51.3.Valen a MM